Copalic acid analogs down-regulate androgen receptor and inhibit small chaperone protein. Issue 11 (1st June 2017)

• Record Type: Journal Article
• Authors: Idippily, Nethrie D.; Zheng, Qiaoyun; Gan, Chunfang; Quamine, Aicha; Ashcraft, Morgan M.; Zhong, Bo; Su, Bin
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 11(2017)
• Page Start: 2292
• Page End: 2295
• Publication Date: 2017-06-01
• Subjects: Copalic acid derivatives -- Small chaperone protein -- Client protein -- AR; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.04.046
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A series of copalic acid analogs was synthesized. Some analogs showed good potency to down-regulate androgen receptor in prostate cancer cells. They also showed small chaperone inhibitory activity in the in vitro assay. The results indicate that using small molecule chaperone inhibitor to down-regulate androgen receptor could be a potential approach for prostate cancer treatment or prevention. Abstract: Copalic acid, one of the diterpenoid acids in copaiba oil, inhibited the chaperone function of α-crystallin and heat shock protein 27 kD (HSP27). It also showed potent activity in decreasing an HSP27 client protein, androgen receptor (AR), which makes it useful in prostate cancer treatment or prevention. To develop potent drug candidates to decrease the AR level in prostate cancer cells, more copalic acid analogs were synthesized. Using the level of AR as the readout, 15 of the copalic acid analogs were screened and two compounds were much more potent than copalic acid. The compounds also dose-dependently inhibited AR positive prostate cancer cell growth. Furthermore, they inhibited the chaperone activity of α-crystallin as well.