Cytotoxic and antimicrobial indole alkaloids from an endophytic fungus Chaetomium sp. SYP-F7950 of Panax notoginseng .

Two new compounds chetoseminudin F (1) and G (2) together with eleven known compounds were isolated from the solid fermentation products of the endophytic fungus Chaetomium sp. SYP-F7950. The structures of the isolated compounds were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, and HRFABMS experiments. The absolute configurations of chetoseminudin F (1) and G (2) were determined by comparing the electronic circular dichroism (ECD) spectrum with those of the reported references. A plausible biogenetic pathway for compounds 1-6 and 9-13 was proposed. These isolates were also evaluated for their antimicrobial and antitumor activity, revealing that chetoseminudin F (1) displayed more potent cytotoxicity against MDA-MB-231 cells with an IC 50 value of 26.49 μmol L -1 more than the common chemotherapeutic agent (paclitaxel). In antimicrobial assay, compounds 6, 9, 11 and 12 had strong antibacterial activity against Staphylococcus aureus , Bacillus subtilis , Enterococcus faecium and antifungal activity against Candida albicans with minimum inhibitory concentration (MIC) values ranging from 0.12 to 9.6 μg mL -1 ; meanwhile compounds 6, 8, 9 and 12 exhibited strong cytotoxicity with IC 50 values of 2.75-8.68 μmol L -1 against tumor cell lines A549 and MDA-MB-231. In addition, morphological observation showed that treatment with compounds 6, 9 and 12 increased the mean length of B. subtilis by 1.6 to 1.8-fold. In silico molecular docking was applied to study the binding interactions between the compounds and the active sites of filamentous temperature-sensitive protein Z (FtsZ) from B. subtilis . Compounds 6, 9 and 12 displayed the low binding energies, strong H-bond interactions with FtsZ. On the basis of the antimicrobial activities, cellular phenotype observation and docking studies, compounds 6, 9 and 12 are considered to be a promising antimicrobial inhibitor of FtsZ.