New cytotoxic cyclic peroxide acids from Plakortis sp. marine sponge

Abstract

Bioassay-guided fractionation of the extract of Jamaican marine sponge Plakortis sp. followed by preparative TLC and HPLC yielded several known methyl ester cyclic peroxides (1a, 2a, 3a, 4, 5), known plakortides (6,7), known bicyclic lactone (8) and new cyclic peroxide acids (1b, 2b, 3b). The chemical structures were elucidated by extensive interpretation of their spectroscopic data. These natural products showed remarkable in vitro cytotoxicity against several cancer cell lines.

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

“…for C 18 H 32 O 4 m/z 312.44; 1 H and 13 C NMR data were identical in all respects to those previously reported in the literature [28,34,35]. …”

“…Plakortin ( 3 ) eluted at a retention time of 18 min. The structure of the compound was analyzed by NMR spectroscopy and mass spectrometry, and according to literature data [28,34,36], the compound was identified as plakortin. Sub-fraction C was purified by semi-preparative RP-HPLC (Phenomenex Hyperclone 5 µ) using acetonitrile/water 60:30 containing 0.1% formic acid as the mobile phase (flow 2 mL/min).…”

“…For the plakortide H acid and its methyl ester, high cytotoxic effects (IC 50 <0.7 µg/mL) and inactivity (>100 µg/mL), respectively, were found against the cell lines NIH3T3 (mouse embryo fibroblast), SSVNIH3T3 (Simian sarcoma virus-transformed NIH3T3), and KA3IT (virally transformed NIH3T3) [28]. Cytotoxic activity against tumor cells (including CCRF-CEM) was also reported for the acids plakortide M and N [29].…”

“…The Caribbean sponge Plakortis halichondrioides produces endoperoxides which were assumed to be synthesized by the polyketide pathway [26,27]. Similar to artesunate, these metabolites did not only display antimalarial activity, but also cytotoxic activity against several tumor cell lines [28,29,30]. From a sample of this sponge, we isolated plakortide E ( 2 , Figure 1) and found that it was also active against trypanosomes [31].…”

Structural diversity and chemical synthesis of peroxide and peroxide-derived polyketide metabolites from marine sponges

“…1). 6,7,13,[51][52][53][54][55][56][57][58][59][60][61][62] Following global interest in antimalarial peroxide natural products such as artemisinin, 63,64 compounds in this class are routinely screened for in vitro activity against strains of Plasmodia (Section 5.1). 11,12,65,66 Testing for cytotoxic action against cancer cell types is also commonplace (Section 5.2).…”