Thiazolidone derivatives as inhibitors of chikungunya virus

• Aralkylidene derivatives of thiazolidinone (1–20) were screened for their anti-chikv activity.
• Five compounds (7, 8, 9, 16 & 19) were found to be active at lower μM concentrations.
• Compounds with polar substitution in (hetero)aryl portion were found to be inactive.
• Docking simulation suggests the inhibition of Chikv nsp2 protease inhibition.

A series of arylalkylidene derivatives of 1,3-thiazolidin-4-one (1–20) were synthesized and tested for their antiviral activity against chikungunya virus (LR2006_OPY1) in Vero cell culture by CPE reduction assay. Five compounds (7–9, 16 and 19) were identified to have anti-ChikV activity at lower micro molar concentration. The compounds 7, 8, 9, 16 and 19 inhibited the virus at 0.42, 4.2, 3.6, 40.1 and 6.8 μM concentrations respectively. Molecular docking simulation has been carried out using the available X-ray crystal structure of the ChikV nsp2 protease, in order to elucidate the possible mechanism of action. Interaction of ligands with ChikV nsp2 protease (PDB Code: 3TRK) suggested the possible mechanism of protease inhibition to act as potent anti-ChikV agents.

A series of twenty aralkylidene derivatives of thiazolidinone (1–20) were evaluated for anti-chikv activity. 5-[(2-methylphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one (7) was found to have IC50 of 0.42 μM.Figure optionsDownload as PowerPoint slide