Chemistry of renieramycins. Part 8: synthesis and cytotoxicity evaluation of renieramycin M-jorunnamycin A analogues.

Abstract Twenty-four ester analogues of renieramycin M ( 1m ) were prepared from jorunnamycin A ( 3a ), which was easily transformed from marine natural 1m in three steps. These analogues, along with 1m itself, cyanojorumycin ( 2b ), and jorunnamycins A ( 3a ) and C ( 3b ), were evaluated in vitro for cytotoxicity by measuring IC 50 values through the 3-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay using human HCT116 colon carcinoma and MDA-MB-435 breast carcinoma cell lines. Nitrogen-containing heterocyclic ester derivatives 9a – f showed similar in vitro cytotoxicity to 1m , whereas the other derivatives were slightly less cytotoxic than 1m . 2′-Pyridinecarboxylic acid ester derivative ( 9c ) exhibited a threefold increase in cytotoxicity relative to 1m .