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

Abstract

BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionThe 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.

Date Palm Trees Root-Derived Endophytes as Fungal Cell Factories for Diverse Bioactive Metabolites

“…This result prompted us to tentatively characterize fungal extract metabolites using high-resolution LC-MS analysis [ 37 ]. LC-MS analysis revealed the presence of numerous metabolites that were reported to have antimicrobial [ 38 , 39 ], anti-diabetic [ 40 ], anti-haemolytic [ 41 ], anti-inflammatory [ 42 , 43 ], anti-obesity [ 44 ], and cytotoxic activities [ 45 ] in both fungi. GC-MS analysis also proved effective in recovering already characterized VOCs with antimicrobial [ 46 ], anti-haemolytic [ 42 ], anti-inflammatory [ 47 ], anti-obesity [ 48 ] and cytotoxic activities [ 49 ].…”

Antibacterial activity of endophytic fungus, Penicillium griseofulvum MPR1 isolated from medicinal plant, Mentha pulegium L.

“…The increasing resistance of pathogenic microorganisms to antibiotics in the world, and recently in Algeria, leading to the resurgence of more complex infections (Baba Ahmed-Kazi Tani and Arlet, 2014), has pushed researchers to discover new bioactive molecules. The capacity of endophytic fungi to biosynthesize bioactive secondary metabolites (more than 20.000 bioactive molecules) (Marson Ascêncio et al, 2014) and their various biological activities such as antimicrobial, anti-viral, anticancer, antioxidant, antidiabetic, and antiinflammatory activity (Sadrati et al, 2013;Bashyal et al, 2014;Shah et al, 2015;Jouda et al, 2016a;Pan et al, 2016;Singh and Kaur 2016;Yao et al, 2017) have made this fungus to be important, as an important source of new bioactive secondary metabolites potentially useful for human medicine and other domains.…”

Natural Polyketides Isolated from the Endophytic Fungus Phomopsis sp. CAM212 with a Semisynthetic Derivative Downregulating the ERK/IκBα Signaling Pathways

“…One of the isolates, CAM212, was selected for further studies based on its morphotype and the LC-MS profile of its crude extract from small-scale fermentation. Identification of the producing strain was carried out according to our previous description [7,30].…”

“…The metabolites produced can be exchanged between endophytic fungi and their host plants. Both plants and endophytic fungi are a rich source of bioactive secondary metabolites with diverse structures including polyketides, alkaloids, phenylpropanoids, terpenoids, and phenols, among others [6,7]. Various compounds such as phomopsichalasin, phomoxanthones A and B, and phomoarcherins A-C were found in the Phomopsis genus [8][9][10].…”