Objective: The emergence of malaria as a global health problem over the past few decades, accompanied by the rise of chemoresistant strains ofPlasmodium falciparum, has emphasized the need for the discovery of new therapeutic drugs against this disease. In this study, enantiomericallyenriched (enantioenriched) analogs of triclosan were synthesized and evaluated for antimalarial activity against P. falciparum cultures.Methods: Enantioselective dihydroxylation of the olefin in amide seven was performed efficiently using chiral quinine ligand (DHQ)2PHAL to yieldenantioenriched dihydroxy propionamide derivative (+)-1 in moderate yields. In a similar way, the chiral quinidine ligand (DHQD)2PHAL was used asstereoselectivity agent yielded the desired enantioenriched (−)-1. The enantioenriched products were used for further in vitro assay, and accordingly thepercent enantiomeric excess (% ee) was not determined. The structures of compounds were proven by spectral data (1H NMR, 13C NMR, and mass spectra).Results: The phenol moiety at the C1 position of triclosan was chemically substituted with a methoxy group, in conjunction with an introducedstereocenter in a 2,3-dihydroxy-propionamide group at C2’ position. Unmodified triclosan inhibited the P. falciparum cultures with an IC50 value of27.2 μM. By contrast, the triclosan analogs, compounds (+)-1 and (−)-1, inhibited the P. falciparum cultures with IC50 values of 0.034 and 0.028 μM,respectively.Conclusion: Collectively, our preliminary in vitro results suggest that these triclosan analogs have potent antimalarial activity and represent apromising new treatment strategy on further development.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.