Novel oxazine skeletons as potential antiplasmodial active ingredients: Synthesis, in vitro and in vivo biology of some oxazine entities produced via cyclization of novel chalcone intermediates

Abstract

A novel series of 6-(2-chloroquinolin-3-yl)-4-substituted-phenyl-6H-1,3-oxazin-2-amines were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive (MRC-02) as well as chloroquine resistant (RKL9) strains of Plasmodium falciparum. The activity tested was at nanomolar concentration. β-Hematin formation inhibition activity (BHIA₅₀) of oxazines were determined and correlated with antimalarial activity. A reasonably good correlation (r = 0.49 and 0.51, respectively) was observed between antimalarial activity (IC₅₀) and BHIA₅₀. This suggests that antimalarial mode of action of these compounds seems to be similar to that of chloroquine and involves the inhibition of hemozoin formation. Some of the compounds were showing better antimalarial activity than chloroquine against resistant strain of P. falciparum and were also found to be active in the in vivo experiment.

Keywords::

• Chalcones
• Plasmodium falciparum
• antimalarial activity
• oxazines

Acknowledgement

The authors thank Head of Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur (India), for providing necessary laboratory facilities and Director, SAIF Lucknow (India) for providing necessary spectral and biological data of compounds.

Declaration of interest

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