Jean Gustave Tangmouo

Antibacterial activity of some natural products against bacteria expressing a multidrug-resistant phenotype

The present study assessed the antimicrobial activities of various natural products belonging to the terpenoids, alkaloids and phenolics against a collection of Gram-negative multidrug-resistant (MDR) bacteria. The results demonstrated that most of the compounds were extruded by bacterial efflux pumps. In the presence of the efflux pump inhibitor phenylalanine arginine β-naphthylamide (PAβN), the activities of laurentixanthone B (xanthone), plumbagin (naphthoquinone), 4-hydroxylonchocarpin (flavonoid) and MAB3 (coumarin) increased significantly against all studied MDR bacteria. Laurentixanthone B, 4-hydroxylonchocarpin and MAB3 contained the same pharmacophoric moiety as plumbagin. This study indicates that the AcrAB-TolC (Enterobacteriaceae) and MexAB-OprM (Pseudomonas aeruginosa) efflux pumps are involved in resistance of Gram-negative bacteria to most of the natural products.

Efflux pumps are involved in the defense of Gram-negative bacteria against the natural products isobavachalcone and diospyrone.

ABSTRACT The activities of two naturally occurring compounds, isobavachalcone and diospyrone, against documented strains and multidrug-resistant (MDR) Gram-negative bacterial isolates were evaluated. The results indicated that the two compounds exhibited intrinsic antibacterial activity against several Gram-negative bacteria, and their activities were significantly improved in the presence of an efflux pump inhibitor (MIC values decreased to below 10 μg/ml). In addition, the activities of isobavachalcone and diospyrone against various strains exhibiting deletions of the major efflux pump components (AcrAB, TolC) were significantly increased. The overall results indicate that isobavachalcone and diospyrone could be candidates for the development of new drugs against MDR strains and that their use in combination with efflux pump inhibitors reinforces their activity.

Diospyrone, crassiflorone and plumbagin: three antimycobacterial and antigonorrhoeal naphthoquinones from two Diospyros spp.

The aim of this study was to evaluate the antimycobacterial and antigonorrhoeal activities of three naphthoquinones (diospyrone, crassiflorone and plumbagin) from Diospyros canaliculata and Diospyros crassiflora as well as the crude extracts from these plants. The agar disk diffusion assay, broth microdilution method, microplate Alamar blue assay (MABA) and radiometric respiratory technique using the BACTEC 460 TB system were used. Results of the antimycobacterial assays indicated that the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations ranged from 1.22 microg/mL to 39.06 microg/mL for Mycobacterium smegmatis and all studied Mycobacterium tuberculosis strains for the crude extract from D. crassiflora, diospyrone and crassiflorone. Results of the killing rate experiment revealed that a total inhibition effect on M. tuberculosis H37Rv strain was observed at Day 18 for D. crassiflora and Day 21 for the crude extract from D. canaliculata and diospyrone at 4x MIC as determined by MABA. Results of the antigonorrhoeal assay indicated that diospyrone was able to prevent the growth of all studied strains of Neisseria gonorrhoeae. The overall results of this work provide evidence that the studied plant extracts (diospyrone, crassiflorone and plumbagin) might be potential sources of new antimicrobial drugs against tuberculosis and gonorrhoea.

Phytotoxic, antifungal activities and acute toxicity studies of the crude extract and compounds from Diospyros canaliculata

In vitro biological activities including phytotoxic, antifungal activities as well as acute toxicity of the methanol extract, fractions and/or isolated compounds from the stem bark of Diospyros canaliculata were investigated. Well agar diffusion and macrodilution assays were used for investigating the antifungal activity. A phytotoxicity assay was performed against Lemna minor while an acute toxicity assay was performed in mice via oral administration. As a result, plumbagin (5-hydroxy-2-methyl-1,4-naphtoquinone) and two known pentacyclic triterpenes (lupeol and lupenone) were isolated from the extract. With regards the antifungal activities, the inhibition zones varied from 16.51 to 24.86 mm and from 20.50 to 25.10 mm for the extract and plumbagin, respectively. The minimum inhibitory concentrations of the extract and plumbagin ranged between 12.5–25 and 0.78–1.56 µg mL−1, respectively. At 50 µg mL−1, the hexane fraction showed phytotoxic activities similar to paraquat, the standard phytotoxic inhibitor. The extract was found to be non-toxic to mice after administration per os. Based on the current findings, we can conclude that this extract is non toxic, with significant phytotoxic and antifungal properties due to the presence of plumbagin.