In vitro and in silico antimalarial activity of 2-(2-hydrazinyl)thiazole derivatives.
A series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of substitutions at 2-, 4- and 5-positions were synthesized, characterized and evaluated their inhibitory potentials against plasmodium falciparum, NF54, by in vitro blood stage assay. The compounds, ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5-carboxylate, 4d, and 1-{4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazol-5-yl}ethan-1-one, 5d showed significant antimalarial activity with IC50 values of 0.725 μM and 0.648 μM respectively. To understand the mechanism, the binding interactions between 2-(2-hydrazinyl)thiazole derivatives and trans-2-enoyl acyl carrier protein reductase of P. falciparum were studied through docking studies. The half maximal inhibitory concentration (IC50) through docking studies for the compounds, 4d and 5d were found to be 22.88 μM and 631.84 μM respectively.
Department of Chemistry, Pondicherry University, Puducherry 605 014, India.
Parameshwar
P
Makam
Division of Nematology, Indian Agricultural Research Institute, New Delhi 110012, India.
Prasoon Kumar
PK
Thakur
Department of Chemistry, Pondicherry University, Puducherry 605 014, India. Electronic address: tharani.che@pondiuni.edu.in.
Tharanikkarasu
T
Kannan
D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D003198:Computer Simulation; D062105:Molecular Docking Simulation; D010963:Plasmodium falciparum / Q000187:drug effects*; D015800:Protozoan Proteins / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D015800:Protozoan Proteins; D013844:Thiazoles
2-Chlorobenzaldehyde (PubChem CID: 6996); 2-Nitrobenzaldehyde (PubChem CID: 11101); 3-Bromobenzaldehyde (PubChem CID: 76583); 3-Hydroxy-4-methoxybenzaldehyde (PubChem CID: 12127); 4-Chlorobenzaldehyde (PubChem CID: 7726); 4-Hydroxy-3-methoxybenzaldehyde (PubChem CID: 1183); 4-Methoxybenzaldehyde (PubChem CID: 31244); Acetophenone (PubChem CID: 7410); Antimalarial activity; Benzaldehyde (PubChem CID: 240); Enoyl-ACP reductase; In silico analysis; In vitro blood stage assay; Plasmodium falciparum; Thiazole; Thiosemicarbazide (PubChem CID: 2723789)