Potential role of CI-679 against artemisinin-resistant <i>Plasmodium falciparum</i>

Abstract

Purpose: To investigate the role of nitroquine (CI-679) against artemisinin-resistant Plasmodium falciparum (P. falciparum) C580Y strain. Methods: Antimalarial activity of CI-679 against blood stages in Plasmodium yoelii (P. yoelii) - infected BALB/c mice model was first  identified. Thereafter, in vitro assays were performed to investigate the inhibitory activity against blood stages of artemisinin-sensitive P.  falciparum 3D7 strain. Finally, the potential effect of CI-679 was also investigated on artemisinin-resistant P. falciparum, which was constructed by introducing C580Y mutation in K13 of the 3D7 using the CRISPR-CAS9 technology. Results: CI-679 significantly suppressed  the growth of rodent malaria parasite, P. yoelii BY265, in a dose-dependent manner, and also inhibited the development of  the parasites in mice (p < 0.05). Furthermore, CI-679 efficiently inhibited the growth of artemisinin-sensitive P. falciparum 3D7 in vitro, with more sensitivity against late phase of blood stages (p < 0.05). Also, CI-679 suppressed the development of artemisinin-resistant P.  falciparum C580Y strain, and the inhibitory effect was comparable to that of artemisinin-sensitive 3D7 strain. Conclusion: CI-679 exhibits  potent antimalarial activity against blood stages of P. yoelii BY265 in vivo, and both artemisinin-sensitive P. falciparum 3D7 and  artemisinin-resistant P. falciparum C580Y in vitro. Further pharmacokinetic properties, tolerability and safety of the compound need to be  investigated to support this claim.