title: Antimalarial evaluation and docking studies of hybrid phenylthiazolyl-1,3,5-triazine derivatives: a novel and potential antifolate lead for Pf-DHFR-TS inhibition.
abstract: Present communication deals with the docking study of hybrid phenyl thiazolyl-1,3,5-triazine analogues (1a-36d) on three selected different binding site viz., α, β and γ of wild type Pf-DFHR-TS. In admiration of excellent H-bond scoring, with regard to cycloguanil and to a large extent similar scoring with WR99210, compound 4a, 12b, 21c, 23c, 28d, 29d, 34d, and 35d were selected for in vitro antimalarial activity against 3D7 strain of Plasmodium falciparum. Findings from the study disclose that a significant correlation was exist between in vitro results and in silico prediction (r(2)=0.543). Furthermore, investigation of structure-activity relationships elucidate crucial structural requirement for site specific binding of ligands.
authors.affiliation: Faculty of Pharmacy, Uttarakhand Technical University, Dehradun, Uttarakhand 248007, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Gahtori
authors.forename: Surajit K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Pratap
authors.initials: P
authors.lastname: Parida
authors.forename: Anil
authors.initials: A
authors.lastname: Prakash
authors.forename: Kabita
authors.initials: K
authors.lastname: Gogoi
authors.forename: Hans Raj
authors.initials: HR
authors.lastname: Bhat
authors.forename: Udaya Pratap
authors.initials: UP
authors.lastname: Singh
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology; D012984:Software; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D005493:Folic Acid Antagonists; D008024:Ligands; D014227:Triazines