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, including¹H,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 µM. Cytotoxicity test revealed CC50 values of the compound were more than 20 µg/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.