title: Quinoline-pyrimidine hybrids: synthesis, antiplasmodial activity, SAR, and mode of action studies.
abstract: For the treatment of malaria which affects nearly 200 million people each year and the continued exacerbation by the emergence of drug resistance to most of the available antimalarials, the "covalent bitherapy" suggests hybrid molecules to be the next-generation antimalarial drugs. In this investigation, new hybrids of 4-aminoquinoline and pyrimidine moieties that show antiplasmodial activity in the nM range against chloroquine-resistant as well as chloroquine-sensitive strains of Plasmodium falciparum have been prepared. Cytotoxicity evaluation and mode of action of most potent hybrid molecule have been conducted.
authors.affiliation: Department of Chemistry, UGC Centre of Advance Study-I, Guru Nanak Dev University , Amritsar, Punjab 143005, India.
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Singh
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kaur
authors.forename: Peter
authors.initials: P
authors.lastname: Smith
authors.forename: Carmen
authors.initials: C
authors.lastname: de Kock
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry; D004351:Drug Resistance; D006418:Heme / Q000737:chemistry; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D000998:Antiviral Agents; D011743:Pyrimidines; D014867:Water; D006418:Heme; D002738:Chloroquine; D004247:DNA