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

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 4.05pg/mL. The best biological profile (IC50 =0.77 mu g/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 light against malaria infections and multidrug resistance problems.

Automated summary

A series of 3-substituted-2-hydroxy-1,4-naphthoquinone derivatives were successfully synthesized by Mannich reaction and evaluated for their in-vitro antimalarial activity. Ten derivatives showed good activity, with compound 1 exhibiting the best biological profile. These active Mannich components could potentially be used as promising antimalarial agents against malaria infections and multidrug resistance.