title: Identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. The ChemBridge database.
abstract: Trypanosomiasis, leishmaniasis, and malaria are major parasitic diseases in developing countries. The existing chemotherapy of these diseases suffers from lack of safe and effective drugs and/or the presence of widespread drug resistance. Cysteine proteases are exciting novel targets for antiparasitic drug design. Virtual screening was performed in an attempt to identify novel druglike nonpeptide inhibitors of parasitic cysteine proteases. The ChemBridge database consisting of approximately 241 000 compounds was screened against homology models of falcipain-2 and falcipain-3 in three consecutive stages of docking. A total of 24 diverse inhibitors were identified from an initial group of 84, of which 12 compounds appeared to be dual inhibitors of falcipain-2 and falcipain-3. Four compounds showed inhibition of both the malarial cysteine proteases as well as Leishmania donovani cysteine protease.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Mississippi, University, Mississippi 38677-1848, USA.
authors.forename: Prashant V
authors.initials: PV
authors.lastname: Desai
authors.forename: Akshay
authors.initials: A
authors.lastname: Patny
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Sabnis
authors.forename: Babu
authors.initials: B
authors.lastname: Tekwani
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenthal
authors.forename: Anuradha
authors.initials: A
authors.lastname: Srivastava
authors.forename: Mitchell
authors.initials: M
authors.lastname: Avery
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000302:isolation & purification; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D007893:Leishmania donovani / Q000737:chemistry / Q000187:drug effects; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3