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.

Keywords::

• Quinoline-N-oxide
• antimalarial agents
• heme polymerization
• P. falciparum

Acknowledgements

The authors thank the Director, CDRI for the support and the SAIF for the spectral data. One of the authors (V.R.S.) thanks the CSIR, New Delhi for Senior Research Fellowship. CDRI communication no. 93/2012/SBK.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.