Synthesis and Bacteriostatic Activities of Bis(thiourea)‎ Derivatives with Variable Chain Length

Abstract EN

A series of 1,4-bis(decoxyphenyl)carbamothioyl-terephthalamide derivatives was successfully synthesised by reaction of benzene-1,4-dicarbonyl isothiocyanate intermediates with long alkyl chain.

The alkylation was performed via Williamson etherification of 4-acetamidophenol with bromoalkanes.

The synthesised bis(thiourea) derivatives differed in the chain length, C nH2n+1, where n = 10 , 12, and 14.

The structures of all compounds were characterised by elemental CHN analysis, IR, 1H, and 13C NMR spectroscopies.

Bacteriostatic activities of bis(thiourea derivatives which consisted of two folds of N-H, C=O, and C=S and long alkyl chain substituents were carried out against Gram-negative bacteria (Escherichia coli, ATCC 25922) via turbidimetric kinetic method.

Bis(thiourea) derivatives with n = 10 and n = 12 displayed excellent activity against E.

coli with MIC of 135 µg/mL and 145 µg/mL, respectively, while bis(thiourea) derivatives with n = 14 acted as cutoff point with no antibacterial properties.

Similar trend was observed in binding affinity to the active site of enoyl ACP reductase (FabI), which demonstrated binding free energy of - 5.3 Kcal/mol and - 4.9 and - 4.8 Kcal/mol, respectively.