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

Four novel resorcylic acid lactones (RALs), curvulomycins A-D (1-4), and six known congeners were isolated from the Beibu Gulf coral-derived fungus 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 IC 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.