Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents
Document Type
Article
Publication Date
5-1-2024
Abstract
Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrugresistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 +/- 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 +/- 3.37 mu M against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 mu M. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.
Keywords
Plasmodium falciparum, Hydantoin derivatives, Antiplasmodial activity, MRC-5 cells
Divisions
chemistry,Parasit
Funders
TAR UMT Internal Research Grant (UC/I/G2019-00037)
Publication Title
Bioorganic & Medicinal Chemistry Letters
Volume
103
Publisher
Elsevier
Publisher Location
THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND