First pharmacophore-based identification of androgen receptor down-regulating agents: Discovery of potent anti-prostate cancer agents

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• 作者：Puranik Purushottamachar ; Aakanksha Kh ; elwal ; Pankaj Chopra ; Neha Maheshwari ; Lalji K. Gediya ; Tadas S. Vasaitis ; Robert D. Bruno ; Omoshile O. Clement ; Vincent C.O. Njar
• 关键词：Pharmacophore ; Catalyst hypothesis ; Androgen receptor down-regulating agents ; Anti-prostate cancer agents
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 出版时间：15 May 2007
• 年：2007
• 卷：15
• 期：10
• 页码：3413-3421
• 全文大小：855 K

文摘

A qualitative 3D pharmacophore model (a common feature based model or Catalyst HipHop algorithm) was developed for well-known natural product androgen receptor down-regulating agents (ARDAs). The four common chemical features identified included: one hydrophobic group, one ring aromatic group, and two hydrogen bond acceptors. This model served as a template in virtual screening of the Maybridge and NCI databases that resulted in identification of six new ARDAs (EC₅₀ values 17.5–212 μM). Five of these molecules strongly inhibited the growth of human prostate LNCaP cells. These novel compounds may be used as leads to develop other novel anti-prostate cancer agents.