Chemistry of renieramycins. Part 8: Synthesis and cytotoxicity evaluation of renieramycin M–jorunnamycin A analogues

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 IC50 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.

The synthesis of twenty-four ester analogues of renieramycin M, as well as their antitumor activities, is described. 9c exhibited a threefold increase in cytotoxicity relative to 1m.Figure optionsDownload as PowerPoint slide