title: Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies.
abstract: The present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a NF-54 strain of Plasmodium falciparum in vitro and N-67 strain of Plasmodium yoelii in vivo. Among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (14) and 2-(2,6-dichloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (22) exhibited significant suppression of parasitaemia in the in vivo assay. All the analogues were found to form strong complex with haematin and inhibited the β-haematin formation in vitro. These results suggest that these compounds act on heme polymerization target.
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: D000634:Aminoquinolines / Q000737:chemistry*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006418:Heme / Q000737:chemistry*; D006420:Hemeproteins / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D058105:Polymerization; D053778:Thiazolidines / Q000737:chemistry
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D006420:Hemeproteins; D053778:Thiazolidines; C020753:hemozoin; D006418:Heme