First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents.
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 (EC(50) values 17.5-212 microM). 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.
Purushottamachar
Puranik
P
Department of Pharmacology & Experimental Therapeutics, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA.
Khandelwal
Aakanksha
A
Chopra
Pankaj
P
Maheshwari
Neha
N
Gediya
Lalji K
LK
Vasaitis
Tadas S
TS
Bruno
Robert D
RD
Clement
Omoshile O
OO
Njar
Vincent C O
VC
D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015153:Blotting, Western; D002384:Catalysis; D045744:Cell Line, Tumor; D019295:Computational Biology; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue