title: Design, synthesis and antimalarial screening of some hybrid 4-aminoquinoline-triazine derivatives against pf-DHFR-TS.
abstract: Existing antifolate antimalarial drugs have shown resistance due to the mutations at some amino acid positions of Plasmodium falciparum DHFR-TS. In the present study, to overcome this resistance, a new series of hybrid 4-aminoquinoline-triazine derivatives were designed and docked into the active site of Pf-DHFR-TS (PDB i.d. 1J3K) using validated CDOCKER protocol. Binding energy was calculated by applying CHARMm forcefield. Binding energy and the pattern of interaction of the docked compounds were analysed. Fifteen compounds were selected for synthesis based on their binding energy values and docking poses. Synthesized compounds were characterised by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy and were screened for antimalarial activity against 3D7 strain of Plasmodium falciparum.
authors.affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004, India. Electronic address: supsjrt@gmail.com.
authors.forename: Supriya
authors.initials: S
authors.lastname: Sahu
authors.affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004, India.
authors.forename: Surajit Kumar
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam 786004, India.
authors.forename: Junmoni
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Pharmacy, Assam University, Silchar, Assam 788011, India.
authors.forename: Mayurakhi
authors.initials: M
authors.lastname: Dutta
authors.affiliation: Department of Pharmaceutical Sciences, Sam Higginbottom Institute of Agriculture, Technology & Science, Deemed University, Allahabad 211007 India.
authors.forename: Hans Raj
authors.initials: HR
authors.lastname: Bhat
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D020128:Inhibitory Concentration 50; D008279:Magnetic Resonance Imaging / Q000379:methods; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000737:chemistry* / Q000494:pharmacology; D044366:Transition Temperature; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D009097:Multienzyme Complexes; D014227:Triazines; C056930:thymidylate synthase-dihydrofolate reductase; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; C001920:4-aminoquinoline
keywords: Aminoquinoline; Antimalarial; Docking; Hybridisation; Triazine