6533b829fe1ef96bd1289a23

RESEARCH PRODUCT

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

Tanja SchirmeisterSwarna OliHongmei WuGerardo Della SalaValeria CostantinoEan-jeong SeoThomas Efferth

subject

LeukemiaCaribbean spongeplakortideEstersAntineoplastic Agents PhytogenicDrug Resistance MultipleArticle570 Life sciencesPoriferaDioxaneslcsh:Biology (General)Caribbean RegionDrug Resistance NeoplasmCell Line TumorPlakortisAnimalsHumanscytotoxicityDrug Screening Assays Antitumorlcsh:QH301-705.5Acidsendoperoxidemulti-drug resistant leukemia570 Biowissenschaften

description

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 (IC50) values of ca. 0.20 µM for both cell lines.

10.3390/md15030063https://pubmed.ncbi.nlm.nih.gov/28273803