Academic literature on the topic 'Bengamide E'

Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using 1H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the range <0.24 to 62.50 µg/mL. This study establishes the bengamides as potent antitubercular compounds, with the first report of whole-cell antitubercular activity of bengamides P 2 and Q 3.

Bengamides are sponge-derived natural products of mixed biosynthesis (polyketides andamino acids), the first two members, isolated from Jaspidae sponges in coral surrounding Fijiislands, were reported in 1986. The main structural variation is located on the 3-aminocaprolactam moiety, and displays a wide range of biological activities, includingantitumor, antibiotic, and anthelmintic properties. These interesting biological activities havemade bengamides popular targets for synthesis and biological studies. There have been somereports on diverse modifications of the caprolactame unit, and indication that N-substitution oncaprolactam greatly influences the antitumor activity. In this paper, we reported the method forsynthesis of 6 amino lactams containing an additional N-alkyl group (4a-4c) and (8a-8c) forfurther synthesis of new bengamide analogues. Their structures were established by MS andNMR spectroscopies.

The limited success and side effects of the current chemotherapeutic strategies against colorectal cancer (CRC), the third most common cancer worldwide, demand an assay with new drugs. The prominent antitumor activities displayed by the bengamides (Ben), a family of natural products isolated from marine sponges of the Jaspidae family, were explored and investigated as a new option to improve CRC treatment. To this end, two potent bengamide analogues, Ben I (5) and Ben V (10), were selected for this study, for which they were synthesized according to a new synthetic strategy recently developed in our laboratories. Their antitumor effects were analyzed in human and mouse colon cell lines, using cell cycle analysis and antiproliferative assays. In addition, the toxicity of the selected analogues was tested in human blood cells. These biological studies revealed that Ben I and V produced a significant decrease in CRC cell proliferation and induced a significant cell cycle alteration with a greater antiproliferative effect on tumor cell lines than normal cells. Interestingly, no toxicity effects were detected in blood cells for both compounds. All these biological results render the bengamide analogues Ben I and Ben V as promising antitumoral agents for the treatment of CRC.

This thesis explores how the menstruating subject is articulated in contemporary consumer culture and through practices of consumption. This results in an alternate reading of the menstruating subject that brings together broader questions related to modernity and history. Consumption in modernity occupies a troubled place for feminist theorists and activists; considering consumption requires the rejection of assumptions about the consumer as a blank slate on which advertisers and marketers write their products. The assumed passivity of the young female consumer is also readily questioned, particularly in relation to sanitary hygiene products. Using the work of Walter Benjamin, particularly his ideas of „now-time‟, the dialectical image and technological reproducibility, allows for a different type of analysis of the menstruating subject in modernity. Understanding how the past, present and future are constructed in current sanitary hygiene product advertising and branding leads to new ways of accessing the everyday for young women in contemporary Australia. Benjamin‟s literary trope of the fragment is also discussed and used in conjunction with the cultural artefacts of everyday objects and commodities. Looking at the visual and digital media of two brands of sanitary hygiene products Moxie and U by Kotex, framed by an autoethnographic approach, I offer a way of considering menstruation and consumption together whilst also suggesting new possibilities for how we frame the everyday for young women in modernity.

The thesis entitled “-Keto phosphonates from tartaric acid in the total synthesis of ()-4-epi-gabosine A, ()-dihydrokawain-5-ol, ()-bengamide E and Identification of MPK-09: A small molecule that restores the wild type function of mutant p53.’’ demonstrates the utility of -keto phosphonate derived from tartaric acid as a building block in the synthesis of bioactive natural products small molecules of therapeutic importance. The thesis is divided into three sections. Section I of the thesis deals with the utility of new -keto phosphonate 1, derived by desymmetrization of bis-Weinreb amide of L-(+)-tartaric acid (Scheme 1). Scheme 1: (a) MeP(O)(OMe)2, n-BuLi, THF, –78 ˚C, 1.5 h, 91%. A series of functionalized aldehydes were used in the Horner-Wadsworth-Emmons type reaction of phosphonate 2. Under the optimized condition, a series of aldehydes including aryl, aliphatic aldehydes with chiral centers next to the aldehyde functionality underwent facile olefination to yield the , unsaturated ketones in good yields (Scheme 2). Scheme 2. (a) Cs2CO3, aldehyde, iPrOH, rt, 1 h. Application of the synthesized unsaturated ketones in the synthesis of various molecular architectures of therapeutic importance was undertaken. Application of this strategy in the total synthesis of (+)-4-epi-gabosine A and (+)-dihydrokawain-5-ol is delineated. The -keto amides were reduced with good diastereoselectivity with NaBH4 to afford the -hydroxy amide which was transformed to the diene. Ring closing metathesis of the diene led to the cyclohexenone which on deprotection gave ()-4-epi-gabosine A (Scheme 3). The key reactions during the synthesis are Horner-Wadsworth-Emmons reaction, stereoselective reduction and ring closing metathesis as shown in Scheme 3. Scheme 3: Stereoselective total synthesis of ()-4-epi-gabosine A. Dihydrokawain-5-ol 11 is a unique 6-alkyl-5-hydroxy-5,6-dihydropyran-2-one isolated from the methanol extracts of the kava plant (Piper mythisticum), a Polynesian shrub of the pepper family and exhibits promising biological activities. Stereoselective total synthesis of this natural product from tartaric acid is described in this section. Key features of the synthesis include the elaboration of the unsaturated ketone obtained from the phosphonate to the allylic alcohol 8 and further elaboration to the natural product 11 as depicted in Scheme 4. Scheme 4: Total synthesis of (+)-dihydrokawain-5-ol. (Part of this work has been communicated). Section II of the thesis deals with the enantiospecific total synthesis of ()-bengamide E. Bengamide E was isolated from the jaspidase sponges by the Crew research group. Enantiospecific total synthesis of bengamide E was accomplished in 8.5% overall yield in a linear sequence of 10 steps starting from the bis-(dimethylamide) unit of tartaric acid as chiral pool precursor (Scheme 5). Key features of the synthesis includes combination of the addition of 1, 3-dithian-2-yllithium, stereoselective reduction and Horner-Wadsworth-Emmons reaction. Scheme 5: Enantiospecific total synthesis of bengamide E. (This work has been published: Metri, P. K.; Schiess, R.; Prasad, K. R. Chem. Asian. J. 2013, 8, 488). Section III of the thesis deals with MPK-09 and a series of novel lactones, structurally similar to bioactive styryllactones synthesized from tartaric acid and studied their in vitro ability to inhibit the growth and induce apoptosis in human tumor cell lines. It was found that MPK-09 a small molecule in the series is more cytotoxic towards cancer cell lines harboring p53 mutation E285K and R273C. Ectopic expression of p53 plasmids harboring various hotspot mutations, demonstrated that MPK-09 was more effective on the tested p53 mutants compared to the wt p53 harboring cells. The restoration of p53 function was further corroborated by the transactivation of its pro-apoptotic signaling pathways as shown by the induction of p21 and Bax protein expression by western analysis. It was demonstrates that the activity was due to the restoration of the wild type conformation of mutant p53. (Part of this work is published: Metri, P. K.; Naz, S.; Kondaiah, P.; Prasad, K. R. ACS Chem. Biol. 2013, 8, 1429).