Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies

作者：Solomon V Raja; Haq W; Srivastava Kumkum; Puri Sunil K; Katti S B^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, 28(3): 619-626.

DOI：10.3109/14756366.2012.666537

• 4-Aminoquinoline
• CQ analogues
• antimalarial agents
• heme polymerization

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-quinolin4- 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 beta-haematin formation in vitro. These results suggest that these compounds act on heme polymerization target.

• 出版日期2013-6