Cytotoxicity of Endoperoxides from the Caribbean Sponge Plakortis halichondrioides towards Sensitive and Multidrug-Resistant Leukemia Cells: Acids vs. Esters Activity Evaluation.

The 6-epimer of the plakortide H acid (), along with the endoperoxides plakortide E (), plakortin (), and dihydroplakortin () have been isolated from a sample of the Caribbean sponge . To perform a comparative study on the cytotoxicity towards the drug-sensitive leukemia CCRF-CEM cell line and its multi-drug resistant subline CEM/ADR5000, the acid of plakortin, namely plakortic acid (), as well as the esters plakortide E methyl ester () and 6-epi-plakortide H () were synthesized by hydrolysis and Steglich esterification, respectively. The data obtained showed that the acids (, , ) exhibited potent cytotoxicity towards both cell lines, whereas the esters showed no activity (, ) or weaker activity (, ) compared to their corresponding acids. Plakortic acid () was the most promising derivative with half maximal inhibitory concentration (IC values of ca. 0.20 µM for both cell lines.