2. Academic Validation
  3. Cyclopentenone-Containing Tetrahydroquinoline and Geldanamycin Alkaloids from Streptomyces malaysiensis as Potential Anti-Androgens against Prostate Cancer Cells

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

  • J Nat Prod. 2021 Jul 23;84(7):2004-2011. doi: 10.1021/acs.jnatprod.1c00297.
Yuhui Xie 1 2,  Lang Guo 3 4,  Jie Huang 5,  Xiaolong Huang 2,  Ziwen Cong 1 2,  Qianqian Liu 3,  Qianshu Wang 5,  Xiaoyan Pang 1,  Songtao Xiang 4,  Xuefeng Zhou 1 6,  Yonghong Liu 1 6,  Junjian Wang 3,  Junfeng Wang 1 6
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/Innovation Academy of South China Sea Ecology and Environmental Engineering, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
  • 2 Laboratory of Tropical Biological Resources of the Ministry of Education of China, Hainan University, Haikou 570228, China.
  • 3 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 4 Department of Urology Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006,China.
  • 5 Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
  • 6 Sanya Institute of Oceanology, SCSIO, Yazhou Scientific Bay, Sanya 572000, China.
PMID: 34225450 DOI: 10.1021/acs.jnatprod.1c00297
Abstract

Malaymycin (1), a new cyclopentenone-containing tetrahydroquinoline alkaloid, and mccrearamycin E (2), a geldanamycin analogue bearing a rare ring-contracted cyclopentenone moiety, and a C2-symmetric macrodiolide (7) were isolated from Streptomyces malaysiensis SCSIO41397. Their structures including absolute configurations were determined by detailed analyses of NMR and HRMS data and ECD calculations. The occurrence of mccrearamycin E (2) 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 1, 4, 5, and 7 showed cytotoxicity against some or all of the five Cancer cell lines with IC50 values ranging from 0.067 to 7.2 μM. In particular, compound 1 inhibited the growth of C42B and H446 cell lines with IC50 values of 67 and 70 nM, respectively. Malaymycin (1) 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 1 strongly suppressed the expression of AR target genes KLK2 and KLK3 in the C42B and 22RV1 cell lines, which suggested that 1 might be a promising potential lead compound for the development of a treatment for the castration-resistant prostate Cancer (CRPC).

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