Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 209, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2020.112889
Keywords
Antimalarial; Pyridylvinylquinoline; 1,2,3-Triazole; Fast-acting; beta-hematin inhibition; Gametocyte stage
Categories
Funding
- NIH/NIAID [AI131398]
- University of Central Florida
Ask authors/readers for more resources
A series of fast-acting, multistage antimalarial agents were synthesized, with compound 60 showing the strongest antimalarial activity and targeting both life stages of the malarial parasites. The results suggest that compound 60, as a fast-acting antimalarial compound, may serve as a candidate for new antimalarial drugs.
To identity fast-acting, multistage antimalarial agents, a series of pyridylvinylquinoline-triazole analogues have been synthesized via CuAAC. Most of the compounds display significant inhibitory effect on the drug-resistant malarial Dd2 strain at low submicromolar concentrations. Among the tested analogues, compound 60 is the most potent molecule with an EC50 value of 0.04 +/- 0.01 mu M. Our current study indicates that compound 60 is a fast-acting antimalarial compound and it demonstrates stage specific action at the trophozoite phase in the P. falciparum asexual life cycle. In addition, compound 60 is active against both early and late stage P. falciparum gametocytes. From a mechanistic perspective, compound 60 shows good activity as an inhibitor of beta-hematin formation. Collectively, our findings suggest that fast-acting agent 60 targets dual life stages of the malarial parasites and warrant further investigation of pyridylvinylquinoline hybrids as new antimalarials. (c) 2020 Elsevier Masson SAS. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available