title: Molecular modeling and 3D-QSAR studies in 2-aziridinyl-and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives as potential antimalarial agents.
abstract: Malaria is still continuing to be one of the most dreadful diseases of the tropical countries particularly due to the development of resistance to the existing antimalarials. From observed, antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives acting through redox cycling mechanism, molecular modeling and three dimensional-quantitative structure activity relationship (3D-QSAR) studies have been carried out on a set of 63 compounds to identify important pharmacophors. Among several 3D-QSAR models generated, three models with correlation coefficient r > 0.82, match > 0.60 and chance = 0.00 have shown two common biophoric sites: one being the oxygen atom at position 1 of the naphthoquinone ring in terms of pi-population, charge and electron donating ability while the second being the center of the phenyl ring in terms of its 6pi-electrons. In addition to these sites, the models also share two common secondary sites: one positively contributing H-acceptor site while the second site contributing negatively in terms of steric refractivity. All these models showed good agreement between the experimental, calculated and predicted antimalarial activities.
authors.affiliation: Medicinal Chemistry Division, Central Drug Research Institute, (CDRI) Chattar Manzil, Lucknow, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Pandey
authors.forename: N B
authors.initials: NB
authors.lastname: Naware
authors.forename: P
authors.initials: P
authors.lastname: Trivedi
authors.forename: A K
authors.initials: AK
authors.lastname: Saxena
mesh_terms: D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology*; D008288:Malaria / Q000188:drug therapy; D008958:Models, Molecular; D009285:Naphthoquinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D010100:Oxygen / Q000737:chemistry; D011522:Protons; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C460940:2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate; C460939:2-aziridinyl-1,4-naphthoquinonyl sulfonate; D000962:Antimalarials; D009285:Naphthoquinones; D011522:Protons; D013438:Sulfhydryl Compounds; D010100:Oxygen