title: Synthesis, antiplasmodial activity and mechanistic studies of pyrimidine-5-carbonitrile and quinoline hybrids.
abstract: A series of hybrids comprising of 5-cyanopyrimidine and quinoline moiety were synthesized and tested for in vitro antiplasmodial activity against NF54 and Dd2 strains of Plasmodium falciparum. Hybrid bearing m-nitrophenyl substituent at C-4 of pyrimidine displayed the highest antiplasmodial activity [IC50 = 56 nM] against the CQ(R) (Dd2) strain, which is four-fold greater than CQ.
authors.affiliation: Department of Chemistry, UGC-Centre of Advance Study-II, Guru Nanak Dev University, Amritsar 143005, India.
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kaur
authors.affiliation: Rega Institute for Medical Research, KU Leuven, 10 Minderbroedersstraat, B-3000 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.affiliation: Division of Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.affiliation: Division of Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.affiliation: Department of Chemistry, South African Medical Research Council Drug Discovery and Development Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.affiliation: Department of Chemistry, UGC-Centre of Advance Study-II, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: kamaljit.chem@gndu.ac.in.
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Singh
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004267:DNA Viruses / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000737:chemistry; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D000998:Antiviral Agents; D009570:Nitriles; D011743:Pyrimidines; D011804:Quinolines; D006418:Heme; C037219:quinoline
keywords: 4-Aminoquinoline; Antiplasmodial agents; Cytotoxic activity; Heme binding; Hybrid antimalarials; Pyrimidine