title: Cytotoxicity of Endoperoxides from the Caribbean Sponge Plakortis halichondrioides towards Sensitive and Multidrug-Resistant Leukemia Cells: Acids vs. Esters Activity Evaluation.
abstract: 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 spongePlakortis 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.
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany. schirmei@uni-mainz.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schirmeister
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany. swarnoli@uni-mainz.de.
authors.forename: Swarna
authors.initials: S
authors.lastname: Oli
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany. hongmei@uni-mainz.de.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.affiliation: The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, 80131 Napoli, Italy. gerardo.dellasala@unina.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Della Sala
authors.affiliation: The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, via D. Montesano 49, 80131 Napoli, Italy. valeria.costantino@unina.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Costantino
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany. seo@uni-mainz.de.
authors.forename: Ean-Jeong
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: Institute of Pharmacy and Biochemistry, Johannes Gutenberg University Mainz, Staudinger Weg 5, 55128 Mainz, Germany. efferth@uni-mainz.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
mesh_terms: D000143:Acids / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017691:Caribbean Region; D045744:Cell Line, Tumor; D004146:Dioxanes / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004952:Esters / Q000737:chemistry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D047229:Plakortis / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry*
chemical_list: D000143:Acids; D000972:Antineoplastic Agents, Phytogenic; D004146:Dioxanes; D004952:Esters; C000593620:plakortide E; C102701:plakortide H
keywords: Caribbean sponge; cytotoxicity; endoperoxide; leukemia; multi-drug resistant leukemia; plakortide