Статті в журналах: "Antimalaria- Drug"

1

Yousif, M. A., and A. A. Adeel. "Antimalarials prescribing patterns in Gezira state: precepts and practices." Eastern Mediterranean Health Journal 6, no. 5-6 (December 15, 2000): 939–47. http://dx.doi.org/10.26719/2000.6.5-6.939.

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A longitudinal pharmacoepidemiological study on prescribing patterns of antimalarials was conducted in Gezira State, Sudan. Different core drug prescribing indicators were identified, measured and correlated. Chloroquine and quinine were the most frequently prescribed antimalaria drugs but in 44.7% of cases, the dosage was inappropriate and did not conform to standard regimens. Due to variable and unmonitored patterns of drug resistance, most medical practitioners in Sudan tend to follow their own protocols to treat severe cases of malaria rather than conforming to standard regimens. We attribute the emergence of a high rate of resistance to malaria chemotherapy to such practices. We recommend interventions to ensure rational prescribing, and call for the formulation of a national antimalarial drugs policy.

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2

Ujuamala Uloma Ezeani, Penaere Theresa Osahon, and Michael Chukwudi Ezeani. "Pattern of anti-malarial drugs and artemether combination therapy adherence in an institution based medical centre, Nigeria." World Journal of Advanced Research and Reviews 8, no. 3 (December 30, 2020): 162–70. http://dx.doi.org/10.30574/wjarr.2020.8.3.0437.

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The change in policy guidelines for treating uncomplicated malaria became necessary because the therapeutic efficacy of chloroquine and SP had deteriorated. Hence compliance is a necessity to enable effective check on malaria. This work was carried out to evaluate antimalaria drug prescription and to update its usage in line with WHO guideline on Artemeter Combination therapy in a university based medical center. We utilized descriptive, cross-sectional, retrospective study of antimalaria prescriptions purposely carried out among male and female outpatients with mean age of 22.4±2.8 at a University health facility. This comprised all outpatients prescriptions that contained at least one antimalarial drug filed from October 2018 to September 2019. Systematic sampling was used to select the prescriptions. Based on the total number of 1250 prescriptions containing at least one antimalarial drug, a sampling interval of 5 was calculated and simple balloting was used for the first pick. A total number of two hundred and fifty (250) prescriptions containing at least one antimalarial drug were selected for the study. Out of 250 antimalaria prescriptions, usage of ACT class of Artemeter lumefantrine, Artemeter Amodiaquine and Artemeter Piparaqiune were recorded at 45.6%, 10.4% and 9.6% respectively. Triple combination Artemeter lumefantrine and Sulphadoxine-Pyrimethamine was recorded at 20.4% while Sulphadoxine-Pyrimethamine was recorded at 4%. Combination of antimalarial drugs with antibiotics was recorded at 31.2%. This study showed compliance with National Antimalarial Treatment Guideline for the treatment of malaria infection as it regards the use of artemisinin-based combination therapy. The frequency usage of artemeter lumefantrine was proceeding among other ACTs. The frequency in co-prescription of antibiotics with anti-malaria should be guarded to comply with WHO recommendation.

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3

Kocisko, David A., and Byron Caughey. "Mefloquine, an Antimalaria Drug with Antiprion Activity In Vitro, Lacks Activity In Vivo." Journal of Virology 80, no. 2 (January 15, 2006): 1044–46. http://dx.doi.org/10.1128/jvi.80.2.1044-1046.2006.

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ABSTRACT In view of the effectiveness of antimalaria drugs inhibiting abnormal protease-resistant prion protein (PrP-res) formation in scrapie agent-infected cells, we tested other antimalarial compounds for similar activity. Mefloquine (MF), a quinoline antimalaria drug, was the most active compound tested against RML and 22L mouse scrapie agent-infected cells, with 50% inhibitory concentrations of ∼0.5 and ∼1.2 μM, respectively. However, MF administered to mice did not delay the onset of intraperitoneally inoculated scrapie agent, the result previously observed with quinacrine. While most anti-scrapie agent compounds inhibit PrP-res formation in vitro, many PrP-res inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo.

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4

Gil, JP, and E. Gil Berglund. "CYP2C8 and antimalaria drug efficacy." Pharmacogenomics 8, no. 2 (February 2007): 187–98. http://dx.doi.org/10.2217/14622416.8.2.187.

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5

Hede, K. "Antimalaria Drug Offers Antitumor Strategies." JNCI Journal of the National Cancer Institute 103, no. 20 (October 4, 2011): 1490–91. http://dx.doi.org/10.1093/jnci/djr423.

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6

Bradbury, Jane. "Synthetic antimalaria drug enters clinical trials." Lancet Infectious Diseases 4, no. 10 (October 2004): 598. http://dx.doi.org/10.1016/s1473-3099(04)01161-2.

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7

Linda Ekawati, Linda Ekawati, Beta Achromi Nurohmah Beta Achromi Nurohmah, Jufrizal Syahri Jufrizal Syahri, and Bambang Purwono Bambang Purwono. "Substituted 3-styryl-2-pyrazoline Derivatives as an Antimalaria: Synthesis, in vitro Assay, Molecular Docking, Druglikeness Analysis and Admet Prediction." Sains Malaysiana 51, no. 10 (October 31, 2022): 3215–36. http://dx.doi.org/10.17576/jsm-2022-5110-09.

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The synthesis, in vitro antimalarial assay, molecular docking, drug-likeness analysis, and ADMET prediction of substituted 3-styryl-2-pyrazoline derivatives as antimalaria have been conducted. The synthesis of N-phenyl (1a‒3a) and N-acetyl-substituted (1b‒3b) 3-styryl-2-pyrazolines was carried out using dibenzalacetone derivatives and hydrazine hydrate or phenylhydrazine. An in vitro antimalarial assay was conducted against the chloroquine-sensitive Plasmodium falciparum 3D7 strain, while molecular docking was performed toward the crystal protein of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) (PDB ID: 1J3I). Furthermore, the prediction of drug-like properties was determined by assessing Lipinski’s rules, and the pharmacokinetic parameters were also studied in-silico, including absorption, distribution, metabolism, excretion, and toxicity (ADMET). The in vitro assay showed that 3a (IC50 0.101 µM) has excellent antimalarial activity, followed by 2a (0.177 µM), and 1b (0.258 µM). Molecular docking has supported the in vitro assay by showing the lowest CDOCKER energy for 3a (‒56.316 kcal/mol), then 2a (‒51.2603 kcal/mol), and 1b (‒48.8774 kcal/mol). The drug-like properties showed that all of the prepared compounds were acceptable based on Lipinski’s rules and predicted to be potentially orally bioavailable. The ADMET analysis provided information that 3a and 2a could be proposed as the best lead antimalarial drugs with further modification to reduce the lipophilicity and toxicity properties.

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8

Peter, Sijongesonke, and Blessing Atim Aderibigbe. "Ferrocene-Based Compounds with Antimalaria/Anticancer Activity." Molecules 24, no. 19 (October 7, 2019): 3604. http://dx.doi.org/10.3390/molecules24193604.

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Malaria and cancer are chronic diseases. The challenge with drugs available for the treatment of these diseases is drug toxicity and resistance. Ferrocene is a potent organometallic which have been hybridized with other compounds resulting in compounds with enhanced biological activity such as antimalarial and anticancer. Drugs such as ferroquine were developed from ferrocene and chloroquine. It was tested in the 1990s as an antimalarial and is still an effective antimalarial. Many researchers have reported ferrocene compounds as potent compounds useful as anticancer and antimalarial agents when hybridized with other pharmaceutical scaffolds. This review will be focused on compounds with ferrocene moieties that exhibit either an anticancer or antimalarial activity.

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9

Muhaimin, Muhaimin, Yusnaidar Yusnaidar, and Hilda Amanda. "Antimalaria Activity of Macaranga Gigantea Leaves Extracts." Journal of The Indonesian Society of Integrated Chemistry 10, no. 2 (April 6, 2019): 23–32. http://dx.doi.org/10.22437/jisic.v10i2.6581.

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The utilization of traditional medicinal plants to medicate malaria caused by Plasmodium is currently more increased along with drug resistance and rising drug prices, and the side effects of using modern medicine. Additionally, Macaranga gigantea plant species have a unique ecological function such as a pioneer plant with good morphological and physiological adaptability to extreme conditions in dealing with natural stress due to pests, temperatures, and UV rays. Therefore, they have a unique biochemical system and a variety of new natural bioactive compounds produced with various activities such as antimicrobial, antioxidant and antiviral in the forest. As the results of previous study, antimalarial activity was shown on the bioactivity of methanol leaves extract of Merkubung (Macaranga gigantea). In short, this study aimed to obtain an active antimalarial fraction of Merkubung leaf (Macaranga gigantea). In this case, fractionation of methanol extract of Merkubung leaf (Macaranga gigantea) was carried out by using different organic solvents followed by an antimalarial bioactivity test using Plasmodium berghei. The results indicated that ethanol fraction of Merkubung left (Macaranga gigantea) had better antimalarial activity than others as a new candidate and supplemental source of antimalarial drugs. Keyword: Macaranga gigantea, malaria, Plasmodium berghei, fraction

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10

Tahir, Iqmal, Mudasir Mudasir, Irza Yulistia, and Mustofa Mustofa. "QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS (QSAR) OF VINCADIFFORMINE ANALOGUES AS THE ANTIPLASMODIAL COMPOUNDS OF THE CHLOROQUINOSENSIBLE STRAIN." Indonesian Journal of Chemistry 5, no. 3 (June 15, 2010): 255–60. http://dx.doi.org/10.22146/ijc.21800.

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Quantitative Structure-Activity Relationship (QSAR) analysis of vincadifformine analogs as an antimalarial drug has been conducted using atomic net charges (q), moment dipole (), LUMO (Lowest Unoccupied Molecular Orbital) and HOMO (Highest Occupied Molecular Orbital) energies, molecular mass (m) as well as surface area (A) as the predictors to their activity. Data of predictors are obtained from computational chemistry method using semi-empirical molecular orbital AM1 calculation. Antimalarial activities were taken as the activity of the drugs against chloroquine-sensitive Plasmodium falciparum (Nigerian Cell) strain and were presented as the value of ln(1/IC50) where IC50 is an effective concentration inhibiting 50% of the parasite growth. The best QSAR model has been determined by multiple linier regression analysis giving QSAR equation: Log (1/IC50) = 9.602.qC1 -17.012.qC2 +6.084.qC3 -19.758.qC5 -6.517.qC6 +2.746.qC7 -6.795.qN +6.59.qC8 -0.190. -0.974.ELUMO +0.515.EHOMO -0.274. +0.029.A -1.673 (n = 16; r = 0.995; SD = 0.099; F = 2.682) Keywords: QSAR analysis, antimalaria, vincadifformine.

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11

Schlagenhauf, Patricia, and Eskild Petersen. "Antimalaria drug resistance: the mono–combi–counterfeit triangle." Expert Review of Anti-infective Therapy 7, no. 9 (November 2009): 1039–42. http://dx.doi.org/10.1586/eri.09.85.

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12

Engwerda, Anthonius H. J., Rick Maassen, Paul Tinnemans, Hugo Meekes, Floris P. J. T. Rutjes, and Elias Vlieg. "Attrition‐Enhanced Deracemization of the Antimalaria Drug Mefloquine." Angewandte Chemie 131, no. 6 (December 21, 2018): 1684–87. http://dx.doi.org/10.1002/ange.201811289.

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13

Friedrich, M. J. "Review Assesses Safety, Effectiveness of Antimalaria Drug Combinations." JAMA 311, no. 11 (March 19, 2014): 1101. http://dx.doi.org/10.1001/jama.2014.2580.

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14

Engwerda, Anthonius H. J., Rick Maassen, Paul Tinnemans, Hugo Meekes, Floris P. J. T. Rutjes, and Elias Vlieg. "Attrition‐Enhanced Deracemization of the Antimalaria Drug Mefloquine." Angewandte Chemie International Edition 58, no. 6 (December 21, 2018): 1670–73. http://dx.doi.org/10.1002/anie.201811289.

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15

Fahmi Rizki Syaban, Mokhamad, Hafidh Alyza Rachman, Azmirfani Diti Arrahman, Nur Hudayana, Jaya Purna Khamid, and Farhan Adi Pratama. "Allium sativum as Antimalaria Agent via Falciapin Protease-2 Inhibitor Mechanism: Molecular Docking Perspective." Clinical and Research Journal in Internal Medicine 2, no. 1 (January 1, 2021): 130–35. http://dx.doi.org/10.21776/ub.crjim.2021.002.01.4.

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Background: Malaria is an endemic disease that can lead to death. Malaria control is a threatening cause of resistance to antimalarial drugs so that renewable therapies are needed to overcome this disease. The chemical compounds of garlic have potential as antimalarial agents, but the mechanism is still unknown. Aim: This research will predict the compounds' molecular mechanism in garlic (Allium sativum) using the in-silico method. Methods: The Insilico method using chemical compounds in Allium sativum were obtained from PubChem, and Falciapain protease-2 was obtained from the Protein Data Bank. Then performed a docking simulation between ligand-protein and analyzed it in 3D. We were used PyRx, Pymol, and DS (Discover Studio) software for analysis and visualization of the interaction of ligandprotein. Results: The results we got, the Alliin compound contained in Allium sativum has the strongest bond with Falcipain protease-2. Allin has fulfilled Lipinski Rule, so Alliin drug-likeness potentially. Alliin has antimalarial activity with its inhibition mechanism against Falcipain protease-2. Conclusion: We recommend this study as a reference for further research on Aliin compounds as antimalarials through in vitro and in vivo methods.

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16

Murtihapsari, Murtihapsari, Mathelda K. Roreng, Apriani Parubak, and Alif Rahman. "Uji Aktivitas Antimalaria dari Spons Xestospongia sp. Asal Pulau Yapen secara In Vivo." Jurnal Kelautan Tropis 24, no. 2 (May 19, 2021): 177–84. http://dx.doi.org/10.14710/jkt.v24i2.10107.

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It is generally admitted that marine sponge has rich of secondary metabolite as alkaloids, peptides and terpene. Those various compounds can be used for antimalarial drug. This study aims to evaluate the in vivo antimalarial activity and to characterize the effectiveness of dose (ED50) of n-hexane extracted from Xestospongia sp. by using the Plasmodium berghei infected to mices. In the present study, we used Peter’s four day suppressive test, where the mice infected with Plasmodium berghei intra peritoneal with a suspension containing infected red blood cell origin from donor mice with parasitemia. Results of present study exhibited that the sponge Xestospongia sp. contains secondary metabolite including tritepenoid/steroid, alkaloid and saponin. Furthermore, an in vivo test revealed the affectivity dose (ED50) was 0.24 mg/kg of body weight. This finding is categorized a signifant decreasing level of parasitemia. Secara umum, spons laut mempunyai kandungan metabolit sekunder seperti alkaloid, peptide dan terpena. Berbagai senyawa tersebut dapat dimanfaatkan sebagai obat antimalaria. Penelitian ini bertujuan untuk mengetahui kandungan kimia dan mengevaluasi aktivitas antimalarial secara in vivo untuk efektivitas dosis (ED50) ekstrak n-heksana dari spons Xestospongia sp. dengan menggunakan Plasmodium berghei yang diinfeksi ke tikus. Penelitian ini digunakan metode the 4-day Supresive Test, dimana mencit yang diinfeksi Plasmodium berghei secara intra peritoneal dengan suspensi yang mengandung sel darah merah terinfeksi yang berasal dari mencit donor. Hasil penelitian ini menunjukkan adanya kandungan metabolit sekunder diantaranya tritepenoid/steroid, alkaloid dan saponin. Selanjutnya, uji in vivo diperoleh nilai ED50 sebesar 0,24 mg/kg BB dikelompokan sangat baik, yang dapat menurunkan tingkat parasitemia secara signifikan. Dengan demikian, spons laut asal pulau Yapen dapat dijadikan sebagai sumber metabolit potensial untuk obat antimalaria.

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17

ROVNER, SOPHIE. "PHARMACEUTICALS Antimalaria drug candidate cures mice in one dose." Chemical & Engineering News 88, no. 36 (September 6, 2010): 13. http://dx.doi.org/10.1021/cen-v088n036.p013a.

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18

Hampton, T. "Collaboration Hopes Microbe Factories Can Supply Key Antimalaria Drug." JAMA: The Journal of the American Medical Association 293, no. 7 (February 16, 2005): 785–87. http://dx.doi.org/10.1001/jama.293.7.785.

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19

Seppa, Nathan. "Drug running: Bust nets suspects in counterfeit antimalaria trade." Science News 173, no. 7 (September 30, 2009): 100–101. http://dx.doi.org/10.1002/scin.2008.5591730705.

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20

Bando, Hironori, and Masahiro Yamamoto. "Antimalaria drug discovery for host factor targeting liver-stage malaria." Medical Entomology and Zoology 69, no. 3 (September 25, 2018): 155–57. http://dx.doi.org/10.7601/mez.69.155.

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21

Arguelho, Maria Lara P. M., Maria Valnice Boldrin Zanoni, and Nelson R. Stradiotto. "Electrochemical Oxidation and Voltammetric Determination of the Antimalaria Drug Primaquine." Analytical Letters 38, no. 9 (July 2005): 1415–25. http://dx.doi.org/10.1081/al-200062218.

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22

Bonko, Massa dit Achille, Marc Christian Tahita, Francois Kiemde, Palpouguini Lompo, Petra F. Mens, Halidou Tinto, and Henk D. F. H. Schallig. "Diagnostic Performance of Plasmodium falciparum Histidine-Rich Protein-2 Antigen-Specific Rapid Diagnostic Test in Children at the Peripheral Health Care Level in Nanoro (Burkina Faso)." Tropical Medicine and Infectious Disease 7, no. 12 (December 15, 2022): 440. http://dx.doi.org/10.3390/tropicalmed7120440.

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(1) Background: Malaria control has strongly benefited from the implementation of rapid diagnostic tests (RDTs). The malaria RDTs used in Burkina Faso, as per the recommendation of the National Malaria Control Program, are based on the detection of histidine-rich protein-2 (PfHRP2) specific to Plasmodium falciparum, which is the principal plasmodial species causing malaria in Burkina Faso. However, there is increasing concern about the diagnostic performance of these RDTs in field situations, and so constant monitoring of their accuracy is warranted. (2) Methods: A prospective study was performed in the health district of Nanoro, where 391 febrile children under 5 years with an axillary temperature ≥37.5 °C presenting at participating health facilities were subjected to testing for malaria. The HRP2-based RDT and expert microscopy were used to determine the diagnostic performance of the former. Retrospectively, the correctness of the antimalaria prescriptions was reviewed. (3) Results: Taking expert malaria microscopy as the gold standard, the sensitivity of the employed RDT was 98.5% and the specificity 40.5%, with a moderate agreement between the RDT testing and microscopy. In total, 21.7% of cases received an inappropriate antimalarial treatment based on a retrospective assessment with expert microscopy results. (4) Conclusion: Malaria remains one of the principal causes of febrile illness in Burkina Faso. Testing with HRP2-based RDTs is inaccurate, in particular, due to the low specificity, which results in an over-prescription of antimalarials, with emerging antimalarial drug resistance as an important risk and many children not being treated for potential other causes of fever.

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23

Golden, Encouse B., Hee-Yeon Cho, Florence M. Hofman, Stan G. Louie, Axel H. Schönthal, and Thomas C. Chen. "Quinoline-based antimalarial drugs: a novel class of autophagy inhibitors." Neurosurgical Focus 38, no. 3 (March 2015): E12. http://dx.doi.org/10.3171/2014.12.focus14748.

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OBJECT Chloroquine (CQ) is a quinoline-based drug widely used for the prevention and treatment of malaria. More recent studies have provided evidence that this drug may also harbor antitumor properties, whereby CQ possesses the ability to accumulate in lysosomes and blocks the cellular process of autophagy. Therefore, the authors of this study set out to investigate whether CQ analogs, in particular clinically established antimalaria drugs, would also be able to exert antitumor properties, with a specific focus on glioma cells. METHODS Toward this goal, the authors treated different glioma cell lines with quinine (QN), quinacrine (QNX), mefloquine (MFQ), and hydroxychloroquine (HCQ) and investigated endoplasmic reticulum (ER) stress–induced cell death, autophagy, and cell death. RESULTS All agents blocked cellular autophagy and exerted cytotoxic effects on drug-sensitive and drug-resistant glioma cells with varying degrees of potency (QNX > MFQ > HCQ > CQ > QN). Furthermore, all quinoline-based drugs killed glioma cells that were highly resistant to temozolomide (TMZ), the current standard of care for patients with glioma. The cytotoxic mechanism involved the induction of apoptosis and ER stress, as indicated by poly(ADP-ribose) polymerase (PARP) cleavage and CHOP/GADD153. The induction of ER stress and resulting apoptosis could be confirmed in the in vivo setting, in which tumor tissues from animals treated with quinoline-based drugs showed increased expression of CHOP/GADD153, along with elevated TUNEL staining, a measure of apoptosis. CONCLUSIONS Thus, the antimalarial compounds investigated in this study hold promise as a novel class of autophagy inhibitors for the treatment of newly diagnosed TMZ-sensitive and recurrent TMZ-resistant gliomas.

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Puspaningtyas, Ayik Rosita. "STUDI FITOKIMIA IRVINGIA MALAYANA SEBAGAI ANTIMALARIA DARI HUTAN MERU BETIRI DALAM RANGKA DRUG DISCOVERY." Jurnal Ilmiah Farmasi Farmasyifa 1, no. 2 (December 28, 2018): 104–18. http://dx.doi.org/10.29313/jiff.v1i2.3340.

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Meru Betiri forest in Jember contains a lot of medicinal plants. Irvingia malayana (Pauh Kijang), which is one of the medicinal plants found, has been proven as an antimalarial. However, phytochemical and antimalarial studies of Irvingia malayana have never been carried out. This study was conducted for an antimalarial Drug Discovery through phytochemical study by isolating the roots, stems, and leaves of Irvingia malayana. From the analysis using FTIR, H-NMR, and GC-MS, it was concluded that the compound in the ethyl acetate extract of Irvingia malayana stem was terpenoids that was included in silymarin group as well as other plants in the genus Irvingia. The melting point of Irvingia malayana isolate was 120-121oC with white crystals. Statistical result of in vivo study showed that each group was significantly different. On day 4 after administration, IC50 showed was 11,827 mg/kgBW and day 3 was 6,927 mg/kgBW. Therefore, 3 days is the maximum duration of administration in reducing plasmodium and shows the most excellent activity as antimalarial. In in vitro study, IC50 of Irvingia malayana (62.855 ug/ml) has weak activity of antiplasmodium compared to chloroquine positive controls containing IC50 (1,114x10-3 ug/ml). Based on the data of in vivo and in vitro antimalarial activities, the compound had no antimalarial activity because the extract consisted of many components that possessed many possible synergetic mechanisms of antimalarial if compared to single compound.Keywords:

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25

Alkandahri, Maulana Yusuf, Nia Yuniarsih, Afiat Berbudi, and Anas Subarnas. "Antimalaria Activities of Several Active Compounds from Medicinal Plants." Pharmacognosy Journal 14, no. 1 (February 22, 2022): 245–52. http://dx.doi.org/10.5530/pj.2022.14.30.

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26

Okokon, Jude E., Aniekan E. Udokpoh, and Bassey S. Antia. "Antimalaria activity of ethanolic extract of Tetrapleura tetraptera fruit." Journal of Ethnopharmacology 111, no. 3 (May 2007): 537–40. http://dx.doi.org/10.1016/j.jep.2006.12.030.

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27

Boehm, Matthias, Peter C. Fuenfschilling, Matthias Krieger, Ernst Kuesters, and Fritz Struber. "An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part I." Organic Process Research & Development 11, no. 3 (May 2007): 336–40. http://dx.doi.org/10.1021/op0602425.

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28

Beutler, Ulrich, Peter C. Fuenfschilling, and Andreas Steinkemper. "An Improved Manufacturing Process for the Antimalaria Drug Coartem. Part II." Organic Process Research & Development 11, no. 3 (May 2007): 341–45. http://dx.doi.org/10.1021/op060244p.

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29

Salahuddin, Salahuddin, Rahmana Emran K, Muhammad Hanafi, Andini Sundowo, Puspa Dewi NL, Nadia Adipratiwi, Titin Ariyani, Erwahyuni Endang Prabandari, and Danang Waluyo. "Sintesis dan Evaluasi Antimalaria In Vitro Turunan Kinin Terhadap Plasmodium falciparum." Jurnal Kefarmasian Indonesia 11, no. 2 (August 31, 2021): 109–20. http://dx.doi.org/10.22435/jki.v11i2.3923.

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Nowadays kinin is the most effective antimalarial drug and its used as an alternative in malaria treatment. However, toxicity of quinine restrict its use as an antimalarial drug. Lipophilicity and long half-life (t½) of quinine that reach 10-20 hours are responsible for its toxicity. The aim of this research is to obtain more polar quinine derivatives by means of hydrogen peroxide reactions to reduce the toxicity. The reactions using hydrogen peroxyde is performed analogously to the procedures reported in the literature. Extract of pure anhydrous kinin is purified in coloumn chromatography followed by structure elucidation. Synthetic product is tested in vitro against Plasmodium falciparum. The characterization of reaction products is performed with proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectroscopy. It showed that the reaction using reagents led to epoxidation of vinyl substituents of chinuclidine ring with 61,08% yields. Antimalarial test against Plasmodium falciparum obtained 1.250-2.500 μg/mL of IC50 value. The IC50 values indicated that the synthesis products were not potential for malaria treatment.

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30

Ajayi, I. O., C. O. Falade, J. D. Adeniyi, and M. O. Bolaji. "The Role of Patent Medicine Sellers in Home Management of Childhood Malaria: A Situational Analysis of Experience in Rural Nigeria." International Quarterly of Community Health Education 21, no. 3 (October 2002): 271–81. http://dx.doi.org/10.2190/569a-xlpx-yf5c-h9hu.

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Patent medicine sellers (PMS) play an important role in supplying the medication needs of the community particularly antimalaria. A situational analysis of the role of PMS in home management of malaria was carried out in four rural local government areas in Southwestern Nigeria using both cross sectional and observational study methods. The results showed that patent medicine stores constituted 76.2% of the medicine shops in the areas. The PMS provided not only drugs but also consultation services. Malaria constituted the commonest fever for which drugs were purchased. The most commonly mentioned drug best for malaria was the 4 aminoquinolone. Many (55.4%) of the PMS have received some form of training on malaria treatment. However, this was carried out in many instances (41.9%) by the shop owners to the apprentice PMS or shopkeepers. Health personnel were mentioned as trainers by only 27% of the PMS. The use of guidelines provided by PMS was infrequent and only 13.8% could produce the guideline at the time of survey. PMS would like to have more training on causes and recognition of malaria and antimalaria dosages. These topics were least taught. The rural PMS is important to the management of malaria. If quality training and supervision is provided to them, home management of malaria should improve.

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Hu, Yingying, Nan Guo, Ting Yang, Jianghong Yan, Wenjun Wang, and Xiang Li. "The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer." Oxidative Medicine and Cellular Longevity 2022 (January 4, 2022): 1–12. http://dx.doi.org/10.1155/2022/1458143.

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Artemisinin (ART) is a bioactive molecule derived from the Chinese medicinal plant Artemisia annua (Asteraceae). ART and artemisinin derivatives (ARTs) have been effectively used for antimalaria treatment. The structure of ART is composed of a sesquiterpene lactone, including a peroxide internal bridge that is essential for its activity. In addition to their well-known antimalarial effects, ARTs have been shown recently to resist a wide range of tumors. The antineoplastic mechanisms of ART mainly include cell cycle inhibition, inhibition of tumor angiogenesis, DNA damage, and ferroptosis. In particular, ferroptosis is a novel nonapoptotic type of programmed cell death. However, the antitumor mechanisms of ARTs by regulating ferroptosis remain unclear. Through this review, we focus on the potential antitumor function of ARTs by acting on ferroptosis, including the regulation of iron metabolism, generation of reactive oxygen species (ROS), and activation of endoplasmic reticulum stress (ERS). This article systematically reviews the recent progress in ferroptosis research and provides a basis for ARTs as an anticancer drug in clinical practice.

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Bialangi, Nurhayati, Mohamad Adam Mustapa, Yuszda Salimi, Weny Musa, Ari Widiyantoro, Agus Malik Ibrahim, Boima Situmeang, and Julinton Sianturi. "Evaluation of the Antiplasmodial Properties of <i>Andrographis paniculata</i> (Burm.f.) and <i>Peperomia pellucida</i> (L.) Kunth." Indonesian Journal of Chemistry 23, no. 1 (December 7, 2022): 62. http://dx.doi.org/10.22146/ijc.74481.

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Plasmodium species are the infectious agents that are responsible for malaria, a disease that claims the lives of approximately 400,000 people annually. The fact that drug resistance against malaria is on the rise suggests that new antimalarial compounds need to be discovered. It is well known that medicinal plants present the best opportunity for the identification of novel antimalaria chemicals. Both the Andrographis paniculata (Burm.f.) and Peperomia pellucida (L. Kunth) species have been tested for their antiplasmodial ability against the Plasmodium falciparum strain. The P. pellucida (L. Kunth) species has also been subjected to in vitro and in vivo biological research. P. pellucida was used to isolate the steroid known as 3-hydroxy-24-ethyl-5,22-cholestadiene (1) and the triterpenoid known as 3-hydroxy-9-lanosta-7,24E-dien-26-oic acid (2). Both compounds were then tested for their activity in vitro. In the mice model, triterpenoid 2 had a substantial chemo-suppressive impact.

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Ibraheem, Zaid O., R. Abd Majid, S. Mohd Noor, H. Mohd Sedik, and R. Basir. "Role of Different Pfcrt and Pfmdr-1 Mutations in Conferring Resistance to Antimalaria Drugs in Plasmodium falciparum." Malaria Research and Treatment 2014 (November 11, 2014): 1–17. http://dx.doi.org/10.1155/2014/950424.

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Emergence of drugs resistant strains of Plasmodium falciparum has augmented the scourge of malaria in endemic areas. Antimalaria drugs act on different intracellular targets. The majority of them interfere with digestive vacuoles (DVs) while others affect other organelles, namely, apicoplast and mitochondria. Prevention of drug accumulation or access into the target site is one of the mechanisms that plasmodium adopts to develop resistance. Plasmodia are endowed with series of transporters that shuffle drugs away from the target site, namely, pfmdr (Plasmodium falciparum multidrug resistance transporter) and pfcrt (Plasmodium falciparum chloroquine resistance transporter) which exist in DV membrane and are considered as putative markers of CQ resistance. They are homologues to human P-glycoproteins (P-gh or multidrug resistance system) and members of drug metabolite transporter (DMT) family, respectively. The former mediates drifting of xenobiotics towards the DV while the latter chucks them outside. Resistance to drugs whose target site of action is intravacuolar develops when the transporters expel them outside the DVs and vice versa for those whose target is extravacuolar. In this review, we are going to summarize the possible pfcrt and pfmdr mutation and their role in changing plasmodium sensitivity to different anti-Plasmodium drugs.

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Rokiban, Akhmad, Ramadhan Triyandi, and Karnila Sari. "EVALUATION OF THE USE OF ANTIMALARIA MEDICINES IN HANURA HEALTH CENTRE PESAWARAN DISTRICT PERIOD JANUARY-DECEMBER IN 2018." JFL: Jurnal Farmasi Lampung 9, no. 1 (March 13, 2021): 36–43. http://dx.doi.org/10.37090/jfl.v9i1.330.

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Abstract Malaria is a public health problem in Indonesia, especially those living in isolated areas. This is published in Presidential Regulation No. 5/2010 concerning the National Medium Term Development Plan for malaria endemic areas, which are divided into high, medium and low endemic areas. High endemic if the API is greater than 50 out of 1,000 population in the provinces of Maluku, Papua, North Sumatra and East Nusa Tenggara. Moderate endemic if the API is 1 to less than 50 dari 1,000 population in the provinces of Aceh, Bangka Belitung, Jambi and West Nusa Tenggara. Low endemic if the API is 0-1 per 1,000 population in Kalimantan, Sulawesi, and parts of Java. This study aims to determine the evaluation of the use of antimalarial drugs with the characteristics of age, sex, and type of malaria plasmodium at the Hanura Public Health Centre based on the criteria of the right indication, the right drug, the right dose, the right interval of drug administration (4T). This research is a descriptive research with purposive sampling method. Collection of prescription data and medical records in January-December 2018. The results showed that in cases of Malaria based on age, the most common cases occurred in the age range of 56-65 years, amounting to 99.6%, based on sex experienced in men by 77.41%, based on body weight the most occurred at 41-59 kg at 45.16%, based on the type of plasmodium experienced plasmodium vivax mostly at 84.95%. Based on these data, it was concluded that the evaluation of the use of antimalarial drugs based on 4T criteria was 100% accurate indication, 100% correct drug, 72.04% correct dose, 98.92% correct interval of drug administration. Keywords: Malaria vivax, treatment, Puskesmas, 4T

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Silalahi, Marina. "HUBUNGAN PEMANFAATAN TUMBUHAN PASAK BUMI (Eurycoma longifolia Jack.) SEBAGAI OBAT TRADISIONAL DAN BIOAKTIVITASNYA." Jurnal Pendidikan Matematika dan IPA 10, no. 2 (July 19, 2019): 109. http://dx.doi.org/10.26418/jpmipa.v10i2.31025.

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Pasak bumi (Eurycoma longifolia Jack.) is a species belonging Simarobuaceae has been long used as traditional medicine, which known very well as aphrosidiac. The studies have been conducted to reveal the benefits of E. longifolia through ethnobotany, phytochemical, and bioessay approaches, but the review articles on the its utilization and bioactivity limited. This article is based on scientific articles published on line or off-line, then synthesized so that to be information the relationship between use and bioactivity. Ethnobotany of E. longifolia have been used as a medicine for fever, malaria, improve stamina, antimalarial, antidiabetic, anticancer, aphrodisiac, overcoming erectile dysfunction. Bioactivity of E. longifolia is antiosteoporotic, antimicrobial, aphrodisiac, anticancer, angiogenesis, and hepatoprotective. Eurycomanone has activity as an antimalaria, antipyretic, aphrodisiac, and cytotoxic. The quassinoids, coumarin and glycosides of El have activity increase the production, quality, totality, synthesis and release of spermatozoa. Eurycoma longifolia is very potential to be developed as an antiosteoporotic and aprosidiac drug, but until now most of it is harvested directly from the forest, so to preserve it, we need to study the cultivation method.

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Ugwuja, D. I., U. C. Okoro, S. S. Soman, R. Soni, S. N. Okafor, and D. I. Ugwu. "New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety." Journal of Enzyme Inhibition and Medicinal Chemistry 34, no. 1 (January 1, 2019): 1388–99. http://dx.doi.org/10.1080/14756366.2019.1651313.

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Debnath, C., E. Haslinger, W. Likussar, and A. Michelitsch. "Determination of the antimalaria drug artemether in pharmaceutical preparations by differential pulse polarography." Journal of Pharmaceutical and Biomedical Analysis 41, no. 2 (May 2006): 638–43. http://dx.doi.org/10.1016/j.jpba.2005.12.003.

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Kumar, Nirbhay, and Hong Zheng. "Stage-specific gametocytocidal effect in vitro of the antimalaria drug qinghaosu onPlasmodium falciparum." Parasitology Research 76, no. 3 (1990): 214–18. http://dx.doi.org/10.1007/bf00930817.

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Afaya, Agani, Solomon Mohammed Salia, Frederick Yaw Opare, Samira Ali, and Richard Adongo Afaya. "Patients’ adherence to antimalarial medication; self-report of patients at the Volta regional hospital of Ho, Ghana." International Journal of Research in Medical Sciences 5, no. 10 (September 28, 2017): 4234. http://dx.doi.org/10.18203/2320-6012.ijrms20174552.

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Background: Despite the advancement in malaria treatments and management; malaria morbidity and mortality is still on the increase. This phenomenon has been mostly attributed to the emergence and transmission resistance of the plasmodium parasite to drugs; which is as a result of non-adherence to anti-malaria medication. Therefore, the purpose of this study was to assess patients’ adherence to anti-malarial medications and the factors influencing their adherence in the Volta regional hospital.Methods: A descriptive cross-sectional study was employed. Convenience sampling technique was used in recruiting respondents. Data were collected within a period of 8 weeks from April to May 2017. Data were analyzed using descriptive statistics in the form of frequencies, percentages, mean and standard deviations which was generated by the use of IBM statistical package for social sciences version 23.Results: The average age of respondents surveyed for this study was 32.27±11.09 ranging from of 19 to 68 years. Majority (51.7%) of respondents were females and 76.7% of them being Christians. The study findings revealed that 36.6% of patient were completely adherent to anti-malarial medication. Over 90% of respondents agreed that the malarial medication had bad taste and it was an unpleasant feeling for them taking it.Conclusions: Poor adherence to antimalaria medications could play a role in the future development of drug resistance. As such, identifying ways to improve anti-malarial compliance will help mitigate drug resistance. Therefore, further studies should be carried out on ways to improve patients’ adherence to antimalarial medication.

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Ferreira, Pedro Eduardo, Maria Isabel Veiga, Isa Cavaco, J. Paulo Martins, Björn Andersson, Shaliya Mushin, Abullah S. Ali, et al. "Polymorphism of Antimalaria Drug Metabolizing, Nuclear Receptor, and Drug Transport Genes among Malaria Patients in Zanzibar, East Africa." Therapeutic Drug Monitoring 30, no. 1 (February 2008): 10–15. http://dx.doi.org/10.1097/ftd.0b013e31815e93c6.

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Cahyaningsih, U., S. Sa’diah, W. Syafii, R. K. Sari, A. J. Maring, and A. B. Nugraha. "Comparison of the combinations of water and ethanol extract of Strychnos ligustrina blum wood with Dihydroartemisinin- Piperaquin Phosphate (DHP) as an anti-malaria in mice infected P. berghei ANKA." IOP Conference Series: Earth and Environmental Science 1174, no. 1 (May 1, 2023): 012015. http://dx.doi.org/10.1088/1755-1315/1174/1/012015.

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Abstract One of the most significant global public health issues is malaria. Combination treatment of S. ligustrina blum wood with Dihydroartemisinin-piperaquin phosphate (DHP) as an antimalaria to increase the effectiveness of S. ligustrina blum wood extract. The purpose of this study was to see how effective the combination of aquadest extract (AE) and 25% ethanol extract (EE) of S. ligustrina blum wood with DHP was against P. berghei ANKA. S. ligustrina blum wood extract were extracted by maceration using aquadest and 25% ethanol. The extract formulated into capsules with or without DHP. Fifty DDY mice were divided into 10 groups (n = 5). Group I was infected infected-untreated, group II was received 25 mg/kg BW of dihydroartemisinin and 197 mg/kg BW of piperaquine phospate, and the others group of mice inoculated with 1x106 P. berghei ANKA and treated with 200 mg/kg. Blood samples were taken every day, starting from the first day to the tenth day. The number of parasites and erythrocytes was calculated using the image photoshop program, then the percentage of parasitemia and inhibition was determined. There was no difference between AE and EE in combination with half dose of DHP with DHP control, but significantly different with infection control. S. ligustrina blum wood extract worked synergistic with DHP as an antimalaria with a percentage of inhibition approaching 100% on the 10th day after treatment. S. ligustrina blum wood extract has the potential to be developed as an effective and safe combination antimalaria drug with pure chemical active ingredients.

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Hafid, Achmad Fuad, Nike Puliansari, Nur Suci Lestari, Lidya Tumewu, Abdul Rahman, and Aty Widyawaruyanti. "Skrining Aktivitas Antimalaria Beberapa Tanaman Indonesia Hasil Eksplorasi Dari Hutan Raya Cangar, Batu-Malang, Jawa Timur." JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA 3, no. 1 (August 4, 2017): 7. http://dx.doi.org/10.20473/jfiki.v3i1.4086.

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Background: Malaria is the most important parasitic disease. Malaria control which depends on specific chemotherapy now complicated by resistance of Plasmodium falciparum to most commonly available antimalarial drug. Such situation has heralded the need for alternative antimalarial therapy. Objective: This research aim was to find new antimalarial candidates from some Indonesia plants collected from Cangar National Forest, Batu-Malang, East Java. Methods: Eleven samples of leaves and stem extracts were screened against Plasmodium falciparum 3D7 culture which maintained in RPMI-1640 Medium. Samples tested in concentration of 0.01, 0.1, 1, 10 and 100 µg/ml. Probit analysis was used to determine IC50. Results: In vitro antimalarial activity revealed that only three crude extracts samples from Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract had good antimalarial activity with IC50 value of 0.33, 0.20 and 0.55 µg/ml, respectively. Conclusions: Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract might be a good candidate for antimalarial natural product resources.

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Hafid, Achmad Fuad, Nike Puliansari, Nur Suci Lestari, Lidya Tumewu, Abdul Rahman, and Aty Widyawaruyanti. "Skrining Aktivitas Antimalaria Beberapa Tanaman Indonesia Hasil Eksplorasi Dari Hutan Raya Cangar, Batu-Malang, Jawa Timur." JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA 3, no. 1 (August 4, 2017): 7. http://dx.doi.org/10.20473/jfiki.v3i12016.7-11.

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Background: Malaria is the most important parasitic disease. Malaria control which depends on specific chemotherapy now complicated by resistance of Plasmodium falciparum to most commonly available antimalarial drug. Such situation has heralded the need for alternative antimalarial therapy. Objective: This research aim was to find new antimalarial candidates from some Indonesia plants collected from Cangar National Forest, Batu-Malang, East Java. Methods: Eleven samples of leaves and stem extracts were screened against Plasmodium falciparum 3D7 culture which maintained in RPMI-1640 Medium. Samples tested in concentration of 0.01, 0.1, 1, 10 and 100 µg/ml. Probit analysis was used to determine IC50. Results: In vitro antimalarial activity revealed that only three crude extracts samples from Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract had good antimalarial activity with IC50 value of 0.33, 0.20 and 0.55 µg/ml, respectively. Conclusions: Fraxinus griffithi stem extract, Piper sulcatum leaves extract and Eucalyptus globulus stem extract might be a good candidate for antimalarial natural product resources.

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Okoye, Blessing Ijeoma, Jacintha Chibuogwu Udemba, Chinwendu Augusta Ndugba, Justina Ijeoma Okonkwo, and Ebierinyo Andi Obed. "Evaluation of rational prescribing in a hospital paediatric outpatient clinic in Nigeria." BMJ Paediatrics Open 6, no. 1 (October 2022): e001585. http://dx.doi.org/10.1136/bmjpo-2022-001585.

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BackgroundIrrational prescribing is a continuing public health issue in low/middle-income countries. This study evaluated the drug use pattern of medicines in paediatrics aged below 12 years attending the outpatient paediatric clinic of Bingham University Teaching Hospital, Nigeria.MethodAn observational cross-sectional study was conducted using patients’ medical records who attended the outpatient paediatric clinic from 1 January to 30 April 2022. The WHO prescribing indicators and guidelines for investigating drug use in health facilities were used.ResultA total of 800 prescriptions containing 2723 drugs were analysed, with a mean number of drugs per prescription of 3.4. A total of 651 patients (81.3%) had at least one antibiotic, and the number of encounters with injection was 17.5% (140 patients). Prescribing by generic name was done for 1406 (51.6%) drugs; of the 2723 drugs prescribed, 2441 (89.6%) were from the WHO Pediatric Essential Medication List. In addition, 80% of the prescriptions contained antimalaria. Analgesics/antipyretics were the most frequently prescribed medicine (87.9%).ConclusionThe findings of this study deviated from the WHO recommended standards. There is a need to target paediatric clinics further and enforce national strategies to tackle non-standard prescribing practices among the paediatric population.

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Madu, Uju L., Adepemi O. Ogundeji, Olufemi S. Folorunso, Jacobus Albertyn, Carolina H. Pohl, and Olihile M. Sebolai. "The Repurposing of the Antimalaria Drug, Primaquine, as a Photosensitizer to Inactivate Cryptococcal Cells." Photochem 1, no. 2 (September 7, 2021): 275–86. http://dx.doi.org/10.3390/photochem1020017.

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Cryptococcal cells can manifest skin infections in immunocompromised persons. While it may be easy to diagnose cryptococcal infection, treatment often fails due to the ineffectiveness of current antifungal agents. To this end, the present study explored the repurposing of primaquine (PQ), as a photosensitizer. PDT was carried out using a germicidal ultraviolet (UV) lamp, which has a radiation output of approximately 625 µW/cm2 at a distance of 20 cm. When compared to the non-treated cells, the metabolic activity of cryptococcal cells was significantly (p < 0.05) limited. The photolytic products of PQ were observed to alter the ultrastructure of treated cells. The latter was not incidental, as the same cells were also documented to lose their selective permeability. Importantly, PDT also improved the efficiency of macrophages to kill internalized cryptococcal cells (p ≤ 0.05) when compared to non-treated macrophages. Equally importantly, PDT was not detrimental to macrophages, as their metabolic activity was not significantly (p > 0.05) limited, even when exposed to 20× the MIC (determined for cryptococcal cells) and an exposure time that was 4× longer. Taken together, the results suggest PQ has the potential to control the growth of cryptococcal cells and limit their survival inside the macrophage.

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Buller, Ronit, Matthew L. Peterson, Örn Almarsson, and Leslie Leiserowitz. "Quinoline Binding Site on Malaria Pigment Crystal: A Rational Pathway for Antimalaria Drug Design." Crystal Growth & Design 2, no. 6 (November 2002): 553–62. http://dx.doi.org/10.1021/cg025550i.

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Yetunde, Onaolapo Adejoke, Onaolapo Olakunle James, and Adeyeba Oluwaseyi Adegboyega. "Malaria, Antimalaria Drugs, Drug/Parasite Interactions, and the Brain: A Review of Impacts on Behaviour, Neurochemistry and Structure." Central Nervous System Agents in Medicinal Chemistry 18, no. 3 (October 23, 2018): 173–92. http://dx.doi.org/10.2174/1871524918666180717111520.

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Powles, Mary Ann, John Allocco, Lai Yeung, Bakela Nare, Paul Liberator, and Dennis Schmatz. "MK-4815, a Potential New Oral Agent for Treatment of Malaria." Antimicrobial Agents and Chemotherapy 56, no. 5 (February 6, 2012): 2414–19. http://dx.doi.org/10.1128/aac.05326-11.

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ABSTRACTMalaria continues to have a significant impact on the health of the developing world. Efforts to combat this disease now focus on combination therapy in order to stem the emergence of resistant parasites. Continued efforts are needed to discover and develop new agents for use in combination antimalarial regimens. MK-4815 is a small molecule with antimalarial activity that was identified from a large pharmaceutical compound collection using a semiautomated version of a well-establishedin vitroassay for the erythrocytic stages ofPlasmodium falciparum. In vitrostudies indicate that the compound selectively accumulates in infected red blood cells and is most effective against the metabolically active late trophozoite/early schizont stages. A variety of drug-resistant field isolates ofP. falciparumwere found to be as sensitive to MK-4815 as the wild-type lines. MK-4815 is orally active in aP. bergheimouse model of acute malaria. In this model, where untreated animals succumb to infection 10 to 12 days postinfection, MK-4815 was completely curative when given as a single dose of 50 mg/kg, 2 doses of 25 mg/kg, or 4.5 doses of 12.5 mg/kg. In pharmacokinetic studies with mice and rhesus monkeys, MK-4815 demonstrated oral bioavailability and low clearance. In addition, MK-4815 is inexpensive to synthesize, an important characteristic for providing affordable antimalaria therapy to the developing world. The attractive biological and pharmaceutical profile of MK-4815 demonstrates its potential for use in combination with other agents in the fight against malaria.

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Tapas, Satya, Abhinav Kumar, Sonali Dhindwal, Preeti, and Pravindra Kumar. "Structural analysis of chorismate synthase from Plasmodium falciparum: A novel target for antimalaria drug discovery." International Journal of Biological Macromolecules 49, no. 4 (November 2011): 767–77. http://dx.doi.org/10.1016/j.ijbiomac.2011.07.011.

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Van Tyne, Daria, Alessandro D. Uboldi, Julie Healer, Alan F. Cowman, and Dyann F. Wirth. "Modulation of PF10_0355 (MSPDBL2) Alters Plasmodium falciparum Response to Antimalarial Drugs." Antimicrobial Agents and Chemotherapy 57, no. 7 (April 15, 2013): 2937–41. http://dx.doi.org/10.1128/aac.02574-12.

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ABSTRACTMalaria's ability to rapidly adapt to new drugs has allowed it to remain one of the most devastating infectious diseases of humans. Understanding and tracking the genetic basis of these adaptations are critical to the success of treatment and intervention strategies. The novel antimalarial resistance locusPF10_0355(Pfmspdbl2) was previously associated with the parasite response to halofantrine, and functional validation confirmed that overexpression of this gene lowered parasite sensitivity to both halofantrine and the structurally related antimalarials mefloquine and lumefantrine, predominantly through copy number variation. Here we further characterize the role ofPfmspdbl2in mediating the antimalarial drug response ofPlasmodium falciparum. Knockout ofPfmspdbl2increased parasite sensitivity to halofantrine, mefloquine, and lumefantrine but not to unrelated antimalarials, further suggesting that this gene mediates the parasite response to a specific class of antimalarial drugs. A single nucleotide polymorphism encoding a C591S mutation withinPfmspdbl2had the strongest association with halofantrine sensitivity and showed a high derived allele frequency among Senegalese parasites. Transgenic parasites expressing the ancestralPfmspdbl2allele were more sensitive to halofantrine and structurally related antimalarials than were parasites expressing the derived allele, revealing an allele-specific effect on drug sensitivity in the absence of copy number effects. Finally, growth competition experiments showed that under drug pressure, parasites expressing the derived allele ofPfmspdbl2outcompeted parasites expressing the ancestral allele within a few generations. Together, these experiments demonstrate that modulation ofPfmspdbl2affects malaria parasite responses to antimalarial drugs.

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