Affiliation:
1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Abstract
Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B–E (1–4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1–4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1–4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 μM, respectively, while jejucarbosides B–D (1–3) showed moderate or no cytotoxic effects.
Funder
National Research Foundation of Korea grants funded by the Korean Government
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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