Synthesis, Molecular Docking, and Evaluation of Some New Curcumin Analogs as Antimalarial Agents

https://doi.org/10.22146/ijc.57646

Endang Astuti(1*), Tri Joko Raharjo(2), Putra Boang Manalu(3), Ilham Satria Putra(4), Stephanus Satria Waskitha(5), Junita Solin(6)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, 55281 Yogyakarta, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, 55281 Yogyakarta, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, 55281 Yogyakarta, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, 55281 Yogyakarta, Indonesia
(5) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, 55281 Yogyakarta, Indonesia
(6) Department of Agronomy, Faculty of Agriculture, Universitas Gadjah Mada, Jl. Flora, Yogyakarta 55821, Indonesia
(*) Corresponding Author

Abstract


This research involves the synthesis, antimalarial evaluation, and molecular docking of several curcumin analogs. A total of six curcumin analog compounds were synthesized using aldol condensation using hydrochloric acid and sodium hydroxide catalysts. The synthesized compounds were elucidated using FTIR, 1H-NMR, 13C-NMR, and LC-MS/MS. Subsequently, all curcumin analogs were tested as an antimalarial agent against Plasmodium falciparum 3D7 strain, and their mechanism of action was evaluated through a molecular docking study. Six curcumin analogs, i.e. 2,6-bis(2-hydroxybenzylidene)cyclohexanone; 2,6-bis(2-hydroxybenzylidene)cyclopentanone; 1.5-bis(2-hydroxyphenyl)penta-1,4-diene-3-one; 2,6-bis(3-hydroxybenzylidene)cyclo-hexanone; 2,6-bis(3-hydroxybenzylidene)cyclopentanone; and 1,5-bis(3-hydroxy-phenyl)penta-1,4-diene-3-one have been successfully synthesized. In addition, 2,6-bis(2-hydroxybenzylidene) cyclopentanone demonstrated the lowest IC50 value and binding affinity of 0.04 µM and -7.6 kcal/mol, respectively. Based on molecular docking studies, this compound also showed the most potent antimalarial activity targeted at PfATP6.

Keywords


curcumin analogs; antiplasmodium; aldol condensation; molecular docking

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DOI: https://doi.org/10.22146/ijc.57646

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