Cyclopiumolides A and B, unusual 13-membered macrolides from the deep sea-sourced fungus Penicillium cyclopium SD-413 with antiproliferative activities

Abstract

Cyclopiumolides A (1) and B (2), first representatives of two novel biosynthetic related 13-membered macrolides featuring an uncommon verrucosidinol unit condensed with a spiculisporic acidic moiety, were identified from the fungus Penicillium cyclopium SD-413, which was obtained from the deep-sea sediments collected in the East China Sea. The structures of cyclopiumolides A (1) and B (2) were identified on the basis of extensive NMR spectroscopic and mass spectrometric data analysis. Their relative and absolute configurations were determined by quantum mechanical calculations of ECD spectra comparing with that of experimental curves and by DP4 + NMR data calculations. Compounds 1 and 2 exhibited significant cytotoxic potencies against the tumor cell lines SF126, FaDu, and TE-1 with IC₅₀ values ranging from 5.86 to 17.05 μM. The inhibition modes and binding sites of 1 and 2 were inspected using molecular docking simulations.

Keywords: Cytotoxicity; Deep-sea sediment; Macrolides; Penicillium cyclopium.