Amengor, Cedric Dzidzor, Boateng, Joshua ORCID: https://orcid.org/0000-0002-6310-729X, Biniyam, Prince Danan, Osei, Michael, Ofori-Acheaw, Raymond, Kingsley Harley, Benjamin, Lartey, Michael, Ohene-Adu, Victoria and Zoiku, Felix Kwame (2025) Propargyl Alcohol-Derived 1,2,3-Triazoles demonstrate antiplasmodial activity. ChemistrySelect. ISSN 2365-6549 (Online) (In Press)

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Abstract

Antimicrobial resistance against current malaria therapies is a major driving force for new compounds. This research demonstrates computationally guided synthesis and antiplasmodial properties of novel propargyl alcohol-derived 1,2,3-triazoles namely: 1-(3-fluoro-2-nitrophenyl)-1H-1,2,3-triazol-1-yl) methanol (M32/S1), (1-(o-tolyl)-1H-1,2,3-triazol-5-yl) methanol (M33/S2), (1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl) methanol (M34/S3), (1-(4-nitrophenyl)-1H-1,2,3-triazol 4-yl) methanol (M35/S4), and 4-(4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl) benzoic acid (M36/S5). Of 36 computationally simulated triazoles, these were synthesized based on high binding energies and favorable docking scores. M36/S5 (moderate binding score) was synthesized to verify absolute correlation of hydrogen bonding deduced from molecular docking to the observed antiplasmodial activity. M32/S1, M33/S2, M34/S3, M35/S4 and M36/S5 exhibited highest binding affinity scores/MMGBSA of (-6.50/-37.81), (-6.20/-32.26), (-6.20/-33.20), (-6.00/-37.47) and (-5.52/-22.93) respectively. In vitro screening using SYBR green assay of M32/S1, M33/S2, M34/S3 and M35/S4 against Plasmodium strains (DD2, 3D7) demonstrated potent antimalarial activity comparable to artesunate. Cytotoxicity was studied against human erythrocytes by MTT assay, and no hemolysis was observed. Docking analysis against Plasmepsin II demonstrated molecular interactions with the catalytic residues in the active site of the binding pocket comparable to chloroquine. To assess in vivo antimalarial activity, Plasmodium berghei NK65-infected mice were used. Up until nine days after infection, all five of the studied drugs showed antimalarial action. The 1, 2, 3-triazole, M32/S1 had biological activity, suppressing parasitemia by 61%. In silico ADMET studies revealed suitable pharmacokinetic properties with M32/S1 identified as the most promising for further optimization. The results show the potential of the selected 1,2,3-triazoles to treat malaria caused by Plasmodium falciparum.

Item Type:	Article
Uncontrolled Keywords:	1,2,3-triazoles, antimalarial activity, click chemistry, molecular docking, Plasmepsin II
Subjects:	Q Science > Q Science (General)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	10 Oct 2025 13:40
URI:	https://gala.gre.ac.uk/id/eprint/51215

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