In vitro activities and mechanisms of action of anti-cancer molecules from African medicinal plants: a systematic review.

Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose in vitro anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases Science Direct, PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.

High-Throughput Solid-Phase Assay for Substrate Profiling and Directed Evolution of Transketolase.

Thiamine diphosphate-dependent enzymes, and specifically transketolases, form one of the most important families of biocatalytic tools for enantioselective carbon-carbon bond formation yielding various hydroxyketones of biological interest. To enable substrate profiling of transketolases for acceptance of different donors and acceptors, a simple, direct colorimetric assay based on pH reaction variation was developed to establish a high-throughput solid-phase assay. This assay reduces the screening effort in the directed evolution of transketolases, as only active variants are selected for further analysis. Transketolase activity is detected as bicarbonate anions released from the α-ketoacid donor substrate, which causes the pH to rise. A pH indicator, bromothymol blue, which changes color from yellow to blue in alkaline conditions, was used to directly detect, with the naked eye, clones expressing active transketolase variants, obviating enzyme extraction.

Chlorinated bianthrones from the cyanolichen Nephroma laevigatum.

While depsidones, depsides or dibenzofuran-like compounds dominate the chemical composition of lichens, the cyanolichen Nephroma laevigatum affords a diversity of quinoid pigments represented by chlorinated anthraquinones derived from emodin and new bianthrones resulting from the homo- or heterodimerization of monomers. Bianthrones were pointed out from the dichloromethane extract by MS/MS-based molecular networking, then isolated and characterized on the basis of extensive spectroscopic analyzes and GIAO NMR shift calculation followed by CP3 analyzes.

Wine Phenolic Compounds Differently Affect the Host-Killing Activity of Two Lytic Bacteriophages Infecting the Lactic Acid Bacterium Oenococcus oeni.

To provide insights into phage-host interactions during winemaking, we assessed whether phenolic compounds modulate the phage predation of Oenococcus oeni. Centrifugal partition chromatography was used to fractionate the phenolic compounds of a model red wine. The ability of lytic oenophage OE33PA to kill its host was reduced in the presence of two collected fractions in which we identified five compounds. Three, namely, quercetin, myricetin and p-coumaric acid, significantly reduced the phage predation of O. oeni when provided as individual pure molecules, as also did other structurally related compounds such as cinnamic acid. Their presence was correlated with a reduced adsorption rate of phage OE33PA on its host. Strikingly, none of the identified compounds affected the killing activity of the distantly related lytic phage Vinitor162. OE33PA and Vinitor162 were shown to exhibit different entry mechanisms to penetrate into bacterial cells. We propose that ligand-receptor interactions that mediate phage adsorption to the cell surface are diverse in O. oeni and are subject to differential interference by phenolic compounds. Their presence did not induce any modifications in the cell surface as visualized by TEM. Interestingly, docking analyses suggest that quercetin and cinnamic acid may interact with the tail of OE33PA and compete with host recognition.

Fungal communities associated with Evernia prunastri, Ramalina fastigiata and Pleurosticta acetabulum: Three epiphytic lichens potentially active against Candida biofilms.

Fungal communities associated to three epiphytic lichens active against Candida, were investigated using culture-based methods We hypothetized that associated fungi would contribute to lichens activities. The ability of specific fungi to grow inside or outside lichens was investigated. To detect biogenesis pathways involved in the production of secondary metabolites, genes coding for nonribosomal peptide synthetase (NRPS) and polyketide synthase I (PKS I) were screened by PCR from fungal DNA extracts. Both endo and epilichenic communities were isolated from two fructicose (Evernia prunastri and Ramalina fastigiata) and one foliose (Pleurosticta acetabulum) lichens. A total of 86 endolichenic and 114 epilichenic isolates were obtained, corresponding to 18 and 24 phylogenetic groups respectively suggesting a wide diversity of fungi. The communities and the species richness were distinct between the three lichens which hosted potentially new fungal species. Additionally, the endo- and epilichenic communities differed in their composition: Sordariomycetes were particularly abundant among endolichenic fungi and Dothideomycetes among epilichenic fungi. Only a few fungi colonized both habitats, such as S. fimicola, Cladosporium sp1 and Botrytis cinerea. Interestingly, Nemania serpens (with several genotypes) was the most abundant endolichenic fungus (53% of isolates) and was shared by the three lichens. Finally, 12 out of 36 phylogenetic groups revealed the presence of genes coding for nonribosomal peptide synthetase (NRPs) and polyketide synthase I (PKS I). This study shows that common lichens are reservoirs of diverse fungal communities, which could potentially contribute to global activity of the lichen and, therefore, deserve to be isolated for further chemical studies.