Antimalarial dihydrochalcone isolated from Artocarpus sericicarpus Jarret leaves and in silico investigation against falcipain-2 protein

Aims: To investigate the potential antimalarial plant belonging to the Artocarpus genus, Artocarpus sericicarpus, and isolate the antimalarial active compound from leaves extract.Methods: The isolation of the antimalarial compound was based on bioassay-guided isolation. The compound isolation was conducted by chromatography and identified using spectroscopic techniques, including 1H,13C, and 2D NMR. The compound was tested for its antimalarial activity against Plasmodium falciparum and evaluated for cytotoxicity using several cell lines, including Huh7, HepG2, BHK-21, and Vero cells. In silico investigation of the compound against falcipain-2 protein was conducted as well.Results: Fractionation and purification of dichloromethane leaves extract led to the isolation of a dihydrochalcone compound identified as 1-(2,4-dihydroxyphenyl)-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]propan-1-one. The dihydrochalcone compound exhibited antimalarial activity with an IC50 value of 34.80 mu M. Cytotoxicity test revealed CC50 values of the compound were more than 20 mu g/mL, and the selectivity indexes (SI) were 4.50, 5.52, 3.02, and 6.68 on Huh7, HepG2, BHK-21, and Vero cells, respectively. The CC50 and SI indicated the nontoxic criteria of the compound. In silico investigation showed that the compound could bind to the falcipain-2 active sites. Conclusions: The dihydrochalcone compound identified as 1-(2,4-dihydroxyphenyl)-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)phenyl]propan-1-one was isolated from Artocarpus sericicarpus leaves extract showed antimalarial activity and the ability to bind to the falcipain-2 active sites on in silico investigation.