Antibacterial and cytotoxic cytochalasins from the endophytic fungus Phomopsis sp. harbored in Garcinia kola (Heckel) nut.

BACKGROUND: The continuous emergence of multidrug-resistant (MDR) bacteria drastically reduced the efficacy of our antibiotic armory and consequently, increased the frequency of therapeutic failure. The search for bioactive constituents from endophytic fungi against MDR bacteria became a necessity for alternative and promising strategies, and for the development of novel therapeutic solutions. We report here the isolation and structure elucidation of antibacterial and cytotoxic compounds from Phomopsis sp., an endophytic fungus associated with Garcinia kola nuts. METHODS: The fungus Phomopsis sp. was isolated from the nut of Garcinia kola. The crude extract was prepared from mycelium of Phomopsis sp. by maceration in ethyl acetate and sequentially fractionated by column chromatography. The structures of isolated compounds were elucidated on the basis of spectral studies and comparison with published data. The isolated compounds were evaluated for their antibacterial and anticancer properties by broth microdilution and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods respectively. The samples were also tested spectrophotometrically for their hemolytic properties against human red blood cells. RESULTS: The fractionation of the crude extract afforded three known cytochalasins including 18-metoxycytochalasin J (1), cytochalasins H (2) and J (3) together with alternariol (4). The cytochalasin compounds showed different degrees of antibacterial activities against the tested bacterial pathogens. Shigella flexneri was the most sensitive microorganism while Vibrio cholerae SG24 and Vibrio cholerae PC2 were the most resistant. Ampicillin did not show any antibacterial activity against Vibrio cholerae NB2, Vibrio cholerae PC2 and Shigella flexneri at concentrations up to 512 µg/mL, but interestingly, these multi-drug resistant bacterial strains were sensitive to the cytochalasin metabolites. These compounds also showed significant cytotoxic properties against human cancer cells (LC50 = 3.66-35.69 µg/mL) with low toxicity to normal non-cancer cells. CONCLUSION: The three cytochalasin compounds isolated from the Phomopsis sp. crude extract could be a clinically useful alternative for the treatment of cervical cancer and severe infections caused by MDR Shigella and Vibrio cholerae.

Penialidins A-C with strong antibacterial activities from Penicillium sp., an endophytic fungus harboring leaves of Garcinia nobilis.

Three new polyketides named penialidins A-C (1-3), along with one known compound, citromycetin (4), were isolated from an endophytic fungus, Penicillium sp., harbored in the leaves of the Cameroonian medicinal plant Garcinia nobilis. Their structures were elucidated by means of spectroscopic and spectrometric methods (NMR and HRMS(n)). The antibacterial efficacies of the new compounds (1-3) were tested against the clinically-important risk group 2 (RG2) bacterial strains of Staphylococcus aureus and Escherichia coli. The ecologically imposing strains of E. coli (RG1), Bacillus subtilis and Acinetobacter sp. BD4 were also included in the assay. Compound 3 exhibited pronounced activity against the clinically-relevant S. aureus as well as against B. subtilis comparable to that of the reference standard (streptomycin). Compound 2 was also highly-active against S. aureus. By comparing the structures of the three new compounds (1-3), it was revealed that altering the substitutions at C-10 and C-2 can significantly increase the antibacterial activity of 1.