title: Docking studies and development of novel 5-heteroarylamino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines as potential antimalarials.
abstract: MOE-Dock (Docking software) was used to predict the binding modes of 10 novel and potent 5-substituted amino-2,4-diamino-8-chloropyrimido-[4,5-b]quinolines (compounds I-X) as part of our antimalarial drug development programme. This was done by analyzing the interaction of these compounds with the active sites of 11 enzymes present in Plasmodium falciparum and based on this, effective binding was observed to enzyme P. falciparum glutathione reductase (PfGR). The binding scores for compounds I-X with PfGR were also congruent with their antimalarial activity. Three additional analogs were then designed and synthesized based on the above docking study and the pharmacophoric requirements for this class.
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India. joshiadvait78@yahoo.com
authors.forename: Advait A
authors.initials: AA
authors.lastname: Joshi
authors.forename: C L
authors.initials: CL
authors.lastname: Viswanathan
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D005980:Glutathione Reductase / Q000187:drug effects; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D011804:Quinolines; D005980:Glutathione Reductase