Antibacterial and Cytotoxic Methylthioether-Containing Cytochalasins from Chaetomium globosum AS-506, an Endozoic...

Ten cytochalasin derivatives, including six new methylthioether-containing chaetoglobosins (thiochaetoglobosins A-F, 1-6), a new related congener (18-nor-prochaetoglobosin II, 7), and three known unsulfured counterparts (8-10), were isolated and identified from Chaetomium globosum AS-506, an endozoic fungus isolated from a deep-sea sponge, which was collected from Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive interpretation of the spectroscopic and X-ray crystallographic data, as well as by ECD calculations. Structurally, thiochaetoglobosins A-F (1-6) represent the first examples of chaetoglobosin derivatives containing a methylthioether group in the molecules, while 18-nor-prochaetoglobosin II (7) is the first 18-nor-chaetoglobosin derivative. Precursor incubation experiments with [¹³C-CH₃]-l-methionine confirmed that the thio-linked methyl was derived from methionine, and a new isotope-labeled thiochaetoglobosin (11) was also isolated and identified. Compound 7 exhibited activity against the aquatic pathogenic bacterium Vibrio alginolyticus (MIC = 0.5 μg/mL), comparable to that of the positive control chloramphenicol. The cell morphology of V. alginolyticus was studied by using growth curves and scanning electron microscopy (SEM) data. The results showed that compound 7 could affect the integrity of the membrane to induce bacteriolysis and death of V. alginolyticus. Additionally, compounds 1, 4, 5, 7, and 9 showed cytotoxic activities against several tumor cell lines with IC₅₀ values ranging from 0.72 to 17.66 μM.