Cyclopentenone-Containing Tetrahydroquinoline and Geldanamycin Alkaloids from as Potential Anti-Androgens against Prostate Cancer Cells.

Malaymycin (), a new cyclopentenone-containing tetrahydroquinoline alkaloid, and mccrearamycin E (), a geldanamycin analogue bearing a rare ring-contracted cyclopentenone moiety, and a -symmetric macrodiolide () were isolated from SCSIO41397. Their structures including absolute configurations were determined by detailed analyses of NMR and HRMS data and ECD calculations. The occurrence of mccrearamycin E () bearing a ring-contracted cyclopentenone is rare in the geldanamycin class. All isolated compounds were evaluated for their cytotoxicities against five cancer cell lines. As a result, compounds , , , and showed cytotoxicity against some or all of the five cancer cell lines with IC values ranging from 0.067 to 7.2 μM. In particular, compound inhibited the growth of C42B and H446 cell lines with IC values of 67 and 70 nM, respectively. Malaymycin () significantly induced cell cycle arrest at the G0/G1 phase in C42B cell lines and caused cell shrinkage and inhibited the expression of the androgen receptor (AR) at both the mRNA and protein levels in a dose-dependent manner. Further examination by qRT-PCR analysis showed that strongly suppressed the expression of AR target genes and in the C42B and 22RV1 cell lines, which suggested that might be a promising potential lead compound for the development of a treatment for the castration-resistant prostate cancer (CRPC).