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

Article published in J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 797-809, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1661_11.5.797

Original Article

Lidya Tumewu^1,2, Hilkatul Ilmi², Ratih Dewi Saputri^2,3, Defi Kartika Sari², Adita Ayu Permanasari², Hanifah Khairun Nisa², Saipul Maulana^4,5, Tjitjik Srie Tjahjandarie⁶, Mulyadi Tanjung^2,6, Che Puteh Osman^7,8, Nor Hadiani Ismail^7,8, Aty Widyawaruyanti^2,9, Achmad Fuad Hafid^2,9*

¹Doctoral Program, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

²Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.

³Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Surabaya, Surabaya, Indonesia.

⁴Master of Pharmaceutical Sciences, Faculty of Pharmacy, Airlangga University, Indonesia.

⁵Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Tadulako University, Central Sulawesi, Indonesia.

⁶Natural Product Chemistry Research Group, Organic Chemistry Division, Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, Indonesia.

⁷Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor, Malaysia.

⁸Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia.

⁹Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia.

*E-mail: achmadfuad@ff.unair.ac.id

Abstract

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 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.