One-Pot Synthesis and In Vitro Studies of Calix[4]-2-methylresorcinarene Derivatives as Antimalarial Agents Against Plasmodium falciparum Chloroquine-Resistant Strain FCR-3
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Baiq Ike Nursofia(1), Yehezkiel Steven Kurniawan(2), Jumina Jumina(3*), Harno Dwi Pranowo(4), Eti Nurwening Sholikhah(5), Jeffry Julianus(6), Susalit Setya Wibowo(7), Hana Anisa Fatimi(8), Yoga Priastomo(9), Krisfian Tata Aneka Priyangga(10)
(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(5) Department of Pharmacology and Therapeutics, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(6) Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Sanata Dharma, Yogyakarta 55282, Indonesia
(7) Research Center for Process and Manufacturing Industry Technology, National Research and Innovation Agency (BRIN), KST BJ Habibie, Banten 15314, Indonesia
(8) Pharmacy Study Program, Faculty of Mathematics and Natural Science, Universitas Sebelas Maret, Jl. Ir. Sutami 36A, Surakarta 57126, Indonesia
(9) Department of Chemical Education, Faculty of Mathematics and Natural Science, Universitas Negeri Yogyakarta, Jl. Colombo No. 1, Yogyakarta 55281, Indonesia
(10) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
(*) Corresponding Author
Abstract
Malaria is an endemic disease in Indonesia caused by infection from the Plasmodium parasite. Recently, antimalarial resistance significantly contributed to the decline in the cure rate of malaria sufferers. In this work, three calix[4]resorcinarenes have been synthesized from 2-methylresorcinol and different benzaldehyde derivatives, i.e., 4-chlorobenzaldehyde, 4-methoxybenzaldehyde, and 4-dimethylaminobenzaldehyde through the one-pot synthesis procedure. The calix[4]resorcinarenes synthesis was done through a cyclo-condensation reaction by using HCl 37% as the catalyst and ethanol as the solvent in an one-pot reaction. The structures of the synthesized products were confirmed using Fourier transform infrared, proton-nuclear magnetic resonance, and liquid chromatography-mass spectrometry techniques. The antimalarial activity assay was evaluated against the Plasmodium falciparum FCR-3 strain through an in vitro study. Three synthesized compounds, i.e., C-4-chlorophenylcalix[4]-2-methylresorcinarene, C-4-methoxyphenylcalix[4]-2-methylresorcinarene and C-4-dimethylaminophenylcalix[4]-2-methylresorcinarene have been successfully synthesized in up to 97% yield. The C-4-chlorophenylcalix[4]-2-methylresorcinerene exhibited the most potent antimalarial activity with a half-maximal inhibitory concentration (IC50) value of 2.66 µM against P. falciparum FCR-3 while the C-4-methoxyphenylcalix[4]-2-methylresorcinarene and C-4-dimethylaminophenylcalix[4]-2-methylresorcinarene gave the IC50 values of 23.63 and 13.82 µM, respectively. From the results, it could be concluded that the antimalarial activity of calix[4]-2-methylresorcinarenes was influenced by the type of substituent of aromatic rings at the para position.
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