Discovery of highly oxygenated cytochalasans with antiproliferative activity from an endophytic fungus Boeremia exigua

Eleven cytochalasans (1-11), including six undescribed analogues (1-3 and 5-7) and a new natural product (4), were obtained from the endophytic fungus Boeremia exigua. Their structures and absolute configurations were determined by a combination of extensive spectroscopic techniques, electron circular dichroism (ECD), and single-crystal X-ray diffraction. Boerelasin E (1) represented the first cytochalasan possessing a cis-configured Δ²¹⁽²²⁾ double bond. The growth-inhibitory activities of all the isolates 1-11 against five human tumor cells were examined. Boerelasin E (1) exhibited the most potent inhibitory effect on MCF-7 cells with an IC₅₀ value of 4.89 μM, even about four times lower than positive control cis-platin (IC₅₀ = 20.52 μM). Further mechanistic investigations revealed that 1 could inhibit the complete cell division of MCF-7 cells by arresting them in the G2/M phase and induced Apoptosis.