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 ( 1 ), along with the endoperoxides plakortide E ( 2 ), plakortin ( 3 ), and dihydroplakortin ( 4 ) have been isolated from a sample of the Caribbean sponge Plakortis halichondrioides . 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 ( 5 ), as well as the esters plakortide E methyl ester ( 6 ) and 6-epi-plakortide H ( 7 ) were synthesized by hydrolysis and Steglich esterification, respectively. The data obtained showed that the acids ( 1 , 2 , 5 ) exhibited potent cytotoxicity towards both cell lines, whereas the esters showed no activity ( 6 , 7 ) or weaker activity ( 3 , 4 ) compared to their corresponding acids. Plakortic acid ( 5 ) was the most promising derivative with half maximal inhibitory concentration (IC ₅₀₎ values of ca. 0.20 µM for both cell lines.