Synthesis and Evaluation of 2-Hydroxy-1,4-Naphthoquinone Derivatives as Potent Antimalarial Agents

Abstract

A series of 3-substituted-2-hydroxy-1,4-naphthoquinone derivatives with a variety of side chains were successfully synthesized by Mannich reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with selected amines and aldehydes. All substances (1-16) were evaluated for in-vitro antimalarial activity against strains of Plasmodium falciparum by microculture radioisotope technique. Bioassay data revealed that ten derivatives (1-8,11 and 13) displayed significantly good activity with values of IC₅₀ ranging from 0.77 to 4.05 μg/mL. The best biological profile (IC₅₀ = 0.77 μg/mL) was observed in compound 1, possessing a n-butyl substituted aminomethyl group. Experimental results support the potential use of our active Mannich components as promising antimalarial agents in the fight against malaria infections and multidrug resistance problems.