title: Pharmacophore model for pentamidine analogs active against Plasmodium falciparum.
abstract: Pentamidine and its analogs constitute a class of compounds that are known to be active against Plasmodium falciparum, which causes the most dangerous malarial infection. Malaria is a widespread disease known to affect hundreds of millions of people and presents a perceivable threat of spreading. Hence, there is a need for well-defined scaffolds that lead to new, effective treatment. Here we present a pentamidine-based pharmacophore constructed using GALAHAD that would aid targeted synthesis of leads with enhanced properties, as well as the development of lead scaffolds. The study was supported by high-quality biological in vitro data of 22 compounds against the P. falciparum strains NF54 and K1. The model established reveals the importance of hydrophobic phenyl rings with polar oxygen and amidine substituents and the hydrophobic linking chain for the activity against malaria.
authors.affiliation: Department of Chemistry, Georgia State University, 50 Decatur Street, Atlanta, GA 30303, USA. prashanthathri@gmail.com
authors.forename: Prashanth
authors.initials: P
authors.lastname: Athri
authors.forename: Tanja
authors.initials: T
authors.lastname: Wenzler
authors.forename: Richard
authors.initials: R
authors.lastname: Tidwell
authors.forename: Svetlana M
authors.initials: SM
authors.lastname: Bakunova
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010419:Pentamidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D000981:Antiprotozoal Agents; D010419:Pentamidine