Synthesis of bengamide E analogues and their cytotoxic activity

Article abstract of DOI:10.1016/j.tetlet.2017.03.077

A series of bengamide E analogues were prepared from the corresponding polyketide chain and amino acids via amide coupling reactions. Opening of the polyketide chain lactone ring with α-aminolactams was successfully achieved under microwave irradiation in the presence of sodium 2-ethyl hexanoate. A cytotoxic activity evaluation against a panel of cancer cell lines (KB, HepG-2, Lu-1, MCF-7, HL-60 and Hela) indicated that the 2′R analogues were generally more cytotoxic than the 2′S analogues. Additionally, several analogues exhibited selective inhibition against various cancer cell lines: compounds 32a and 32b selectively inhibited MCF-7 cells, while 33b and 35b were more sensitive toward Lu-1 and HepG-2, respectively. Notably, some of the synthetic analogues possess cytotoxic activities with IC₅₀ values less than 1?μM.