Phytochemical analysis and evaluation of antiplasmodial and cytotoxic activities of Wrightia dubia and Wrightia pubescens traditionally used for malaria treatment in Southeast Asia.

Wrightia dubia and Wrightia pubescens are traditionally used to treat malaria, yet their phytochemical and pharmacological profiles remain underexplored. A preliminary screening of the plant extracts showed promising antiplasmodial activity, warranting further investigation. Thus, this study aims to investigate their phytochemical constituents and their antiplasmodial, cytotoxic, and hemolytic activities. Of the ten extracts screened, three dichloromethane extracts of W. dubia wood, W. dubia twig, and W. pubescens twig demonstrated significant antiplasmodial activity with the IC50 values of 1.89 ± 0.06 μg/mL, 6.38 ± 0.04 μg/mL, and 1.79 ± 0.03 μg/mL, respectively. LC-MS analysis of the active extracts tentatively identified 38 compounds. Exhaustive chromatographic procedures yielded a new natural product, 2-(2'-hydroxyphenyl)quinazolin-4(3H)-one, along with nine known compounds. Tryptanthrin demonstrated significant antiplasmodial activity against the Plasmodium falciparum 3D7 and Dd2 strains, with the IC50 values of 2.50 ± 0.05 μM and 3.14 ± 0.023 μM, respectively. All active extracts (CC50 > 30 μg/mL) and their isolated compounds (CC50 > 10 μM) were non-toxic to HepG2 cell lines. None of the tested samples induced erythrocyte hemolysis at 100 μg/mL. These findings support further in vivo evaluation of tryptanthrin as lead candidate for antimalarial drug development.