title: 4-Aminoquinoline-pyrimidine hybrids: synthesis, antimalarial activity, heme binding and docking studies.
abstract: A series of novel 4-aminoquinoline-pyrimidine hybrids has been synthesized and evaluated for their antimalarial activity. Several compounds showed promising in vitro antimalarial activity against both CQ-sensitive and CQ-resistant strains with high selectivity index. All the compounds were found to be non-toxic to the mammalian cell lines. Selected compound 7g exhibited significant suppression of parasitemia in the in vivo assay. The heme binding studies were conducted to determine the mode of action of these hybrid molecules. These compounds form a stable 1:1 complex with hematin suggesting that heme may be one of the possible targets of these hybrids. The interaction of these conjugate hybrids was also investigated by the molecular docking studies in the binding site of PfDHFR. The pharmacokinetic property analysis of best active compounds was also studied using ADMET prediction.
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: National Center for Natural Products Research, University of Mississippi, MS-38677, USA; Department of Biomolecular Sciences, University of Mississippi, MS-38677, USA; Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.affiliation: National Center for Natural Products Research, University of Mississippi, MS-38677, USA; Department of Biomolecular Sciences, University of Mississippi, MS-38677, USA.
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Prija
authors.initials: P
authors.lastname: Ponnan
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India. Electronic address: dsrawat@chemistry.du.ac.in.
authors.forename: Diwan S
authors.initials: DS
authors.lastname: Rawat
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D006418:Heme / Q000737:chemistry*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D011743:Pyrimidines; D006418:Heme; C001920:4-aminoquinoline
keywords: Aminoquinoline; Antimalarial activity; Docking studies; Heme binding studies