title: Design and synthesis of 3-[(7-chloro-1-oxidoquinolin-4-ylamino)alkyl]-1,3-thiazolidin-4-ones as antimalarial agents.
abstract: A new series of quinoline analogs have been synthesized and found active against P. falciparum in vitro and P. yoelli in vivo. Compounds 8, 10 and 11 exhibited superior in vitro activity compared to chloroquine. Selected compounds 8, 10 and 11 exhibited significant suppression of parasitaemia in vivo assay. These analogs form a complex with hematin and inhibit the β-hematin formation, suggesting that this class of compounds act on a heme polymerization target. Further this study confirms that quinoline ring nitrogen is essential for both transportation of the molecule across the membrane as well as for tight binding to hematin.
authors.affiliation: Division of Medicinal and Process Chemistry, Central Drug Research Institute , Lucknow , India.
authors.forename: V Raja
authors.initials: VR
authors.lastname: Solomon
authors.forename: W
authors.initials: W
authors.lastname: Haq
authors.forename: Kumkum
authors.initials: K
authors.lastname: Srivastava
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.forename: S B
authors.initials: SB
authors.lastname: Katti
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010961:Plasmodium / Q000187:drug effects*; D013329:Structure-Activity Relationship; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D053778:Thiazolidines