Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Potential role of CI-679 against artemisinin-resistant Plasmodium falciparum

Nie Tan¹, Yuemeng Zhao¹, Yan Ding¹, Yong Fu¹, Haoxing Li¹, Jian Zhang¹, Qingfeng Zhang¹, Wenyue Xu²

¹Department of Pathogenic Biology, Army Medical University (The Third Military Medical University), Chongqing 400038, China; ²Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the Ministry of Education of China, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

For correspondence:- Wenyue Xu Email: xuwenyue@tmmu.edu.cn Tel:+8615730267295

Accepted: 4 January 2024 Published: 30 January 2024

Citation: Tan N, Zhao Y, Ding Y, Fu Y, Li H, Zhang J, et al. Potential role of CI-679 against artemisinin-resistant Plasmodium falciparum. Trop J Pharm Res 2024; 23(1):85-99 doi: 10.4314/tjpr.v23i1.11

© 2024 The authors.
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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.

Keywords: CI-679, Nitroquine, Blood stage, Artemisinin-resistant, Plasmodium falciparum