Auswahl der wissenschaftlichen Literatur zum Thema „Justicidin C“

Commiphora gileadensis L. is an important endangered medicinal plant that belongs to the family Burseraceae. In this study, C. gileadensis callus culture was established successfully using mature leaves as explants cultured on Murashige and Skoog (MS) media supplemented with 24.50 μM of indole butyric acid (IBA) and 2.22 μM 6-Benzylaminopurine (BAP) (callus induction media). The obtained callus was maintained on MS medium supplemented with 16.11 μM naphthalene acetic acid (NAA) in combination with 6.66 μM BAP, which resulted in a substantial increase in callus fresh and dry weights. The cell suspension culture was established successfully using liquid callus induction media supplemented with 3.0 mg·L−1 proline. Thereafter, the chemical constituents of different C. gileadensis methanolic extracts (callus, cell suspension, leaves, and seeds) were profiled, and their cytotoxic and antimicrobial properties were investigated. The LC-MS GNPS analyses were applied for chemical profiling of the methanolic plant extracts, and several natural products were identified, including flavonols, flavanones, and flavonoids glycosides, with two unusual families that included puromycin, 10-hydroxycamptothecin, and justicidin B. The methanolic extracts have shown selective antimicrobial and cytotoxic properties against different microbes and cancer cell lines. For instance, leaf extract showed the highest zone of inhibition for Staphylococcus aureus, while cell suspension culture was effective against Staphylococcus epidermidis and Staphylococcus aureus. All extracts showed selective activity against A549 cell lines for the cytotoxicity assay, while the leaf extract had a broad cytotoxic effect against all tested cell lines. This study revealed that C. gileadensis callus and cell suspension cultures can be employed to increase the in vitro formation of biologically active compounds that may have cytotoxicity and antibacterial action against different cancer cell lines and bacterial species. Further studies are required to isolate and identify such constituents that corroborate the observed activities.

Justicidone, a C-5, C-8 dioxo-lignan of the arylnaphthalene type isolated from Justicia hyssopifolia, and its synthetic precursors were tested for the activity against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. Justicidone showed activity against L. braziliensis with an IC50 of 181.90 μM, while, the diasteromeric mixture of one of its synthetic precursors exhibited activity against both parasite strains with an IC50 of 99.27 μM (L. braziliensis) and 181.75 μM (L. amazonensis). This activity has not previously been reported for dibenzylbutyrolactones and dioxo-lignans.

The dioxo-lignans of the arylnaphthalene-type named justicidone (2) and elenodione (3) were obtained from elenoside (1) through a short and efficient semisynthetic process. Justicidone (2), one of its synthetic precursors, 4-(benzo[d][1,3]dioxol-5-yl)-5,6,8-trimethoxy-3a,4-dihydronaphtho[2,3-c]furan-1(3H)-one (9), and the aglycone of elenoside (5) showed cytotoxic activity towards the HL-60 cell line (IC50 = 7.25 μM, 5.41 μM and 2.06 μM, respectively).

Le cancer du sein est la tumeur maligne la plus fréquente chez les femmes, il reste le premier en termes d’incidence (2,1 millions de nouveaux cas dans le monde en 2018) et de phénomènes de résistance des cellules cancéreuses aux différents traitements sont apparue. En raison de son impact majeur sur la population, cette maladie représente un problème de santé publique critique qui nécessite des recherches supplémentaires aux niveaux moléculaires afin de définir son traitement spécifique. Le règne végétal reste une source primordiale pour de nombreux chercheurs afin de trouver de nouvelles molécules biologiquement actives, pouvant amener à la découverte de principes actifs potentiellement intéressants sur le plan thérapeutique. Les principes actifs sont directement isolés des extraits des plantes, ou obtenus par hémisynthèse à partir des molécules d’extraction. C’est dans cette démarche que les travaux réalisés par notre groupe de recherche, dans le domaine de l’extraction et la synthèse de substances antalgiques et anticancéreuses, à partir des plantes utilisées dans la pharmacopée traditionnelle, nous ont conduits à envisager des pharmacomodulations en série sur des analogues de la « Guieranone A », molécule naturelle isolée à partir des feuilles de Guiera senegalensis plante largement utilisée en médecine traditionnelle africaine pour ces propriétés thérapeutiques et qui possède des activités antiprolifératives remarquables sur différents lignées tumorales et en particulier sur le cancer du sein (lignée hormono-dépendante MCF-7, CI50 =3,42 ±0,090 µM ). Nous avons donc développé une approche synthétique permettant la préparation des méthoxynaphtalènes et de méthoxynaphtoquinones. Cette approche utilise comme produit de départ le 3,4-diméthoxy benzaldehyde et met en jeu des réactions de type Stobbe et Wittig-Horner-Emmons. Les réactions de synthèses développées sur cette base, ainsi que les molécules préparées, ont permis de synthétiser également des lignanes et des aza-lignanes, composés d’intérêt biologiques ou / et pharmacologiques très représentés dans de nombreuses plantes aromatiques et médicinales (PAM), du genre Justicia et Vitex. Notre méthode de synthèse a permis la préparation avec de bons rendements, des produits naturels et ses analogues (Justicidine C, Cilinaphthalide B, Méthoxy-vitedoamine A), via une réaction de chloroformylaion suivie d’une réaction de couplage de Suzuki-Miyaura
Breast cancer is the most common malignant tumor in women, and the first in terms of incidence (2.1 million new cases worldwide in 2018). An increasing problem is the resistance of some cancer cells to different treatments. Due to its major impact on the population, this disease represents a critical public health problem that requires additional research at the molecular level in order to define specific therapies. The plant kingdom remains an essential source for many researchers in order to find new biologically active molecules, which can lead to the discovery of active ingredients. It is in this approach that the work carried out by our research group, in the field of the extraction and synthesis of analgesic and anticancer substances from plants used in traditional pharmacopoeia, led us to consider serial pharmacomodulations on analogues of « Guieranone A », a natural molecule isolated from the leaves of the Guiera senegalensis plant which is widely used in traditional African medicine for its therapeutic properties and which has remarkable antiproliferative activities on various tumor lines and in particular on breast cancer (MCF-7 hormone-dependent line, IC50 = 3.42 ± 0.090 µM). We have therefore developed a synthetic approach using 3,4-dimethoxy benzaldehyde as a starting material and involving Stobbe and Wittig-Horner-Emmons reactions. The synthetic reactions developed on this basis, as well as the molecules prepared, have opened a synthetic route to lignans and aza-lignans, compounds of biological and / or pharmacological interest well represented in many aromatic and medicinal plants (AMP), of the genus Justicia and Vitex. By this way, Justicidin C, Cilinaphthalide B, and Methoxy-vitedoamine A were prepared via a chloroformylation reaction followed by a Suzuki-Miyaura coupling reaction