Antiproliferative effects of resorcylic acid lactones from the Beibu Gulf coral-derived fungus Curvularia lunata GXIMD 02512 on prostate cancer cells

Abstract

Four novel resorcylic acid lactones (RALs), curvulomycins A–D (1–4), and six known congeners were isolated from the Beibu Gulf coral-derived fungus Curvularia lunata GXIMD 02512. Their structures including absolute configurations were established by extensive spectroscopic analyses along with experimental and calculated ECD spectra. Structurally, compound 3 harbors a unique γ-pyrone moiety rarely found in the natural RAL family. Notably, curvulomycin D (4) represents the first reported compound of the rare 8-membered RAL derivatives. Compounds 1 and 5 exhibited significant antiproliferative potency against two prostate cancer cell lines, with IC₅₀ values of 9.70 ± 0.77 μM and 7.64 ± 0.46 μM for PC-3 cells and 5.96 ± 0.43 μM and 3.15 ± 0.27 μM for 22Rv1 cells, respectively. Moreover, compound 1 inhibited clonal cell colonies in a dose-dependent manner, blocked the S and G2 phases in the PC-3 cell cycle and the G1 phase in the 22Rv1 cell cycle, which further induced apoptosis in both PC-3 and 22Rv1 cells, indicating its potential as a promising lead compound for anti-prostate cancer therapy.