Synthesis, spectral characterization, antibacterial, cytotoxic evaluation and docking studies of new urea and thiourea derivatives

767-776Isoniazid is one of the main API’s used in the combination treatment of tuberculosis recommended by the WHO. Urea and its derivatives are an important class of heterocyclic compounds that possess a wide range of therapeutic and pharmacological properties, while thiourea is an organosulphur compound in that it resembles urea except that the atom oxygen has been replaced by a Sulphur atom, but the properties of urea and thiourea are significantly different. The current work concerns the synthesis of a new class of urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates in the presence of trimethylamine. The IR and NMR spectral data were performed for the urea and thiourea derivatives of the compounds [(3c & 3f) & (3d & 3e)], respectively. Molecular docking studies of the compounds (3a-h) revealed the binding mode involved in the active site of DNA gyrase. The synthesized urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates were tested for their antibacterial activity against gram-positive and gram-negative bacteria using the “disc diffusion method”. Of all compounds tested, the urea derivatives (3a &3d), the thiourea derivatives (3e & 3g) showed more potent activity than the other compounds. The MTT assay revealed concentration dependent cytotoxic effects over a concentration range 25-200 μg/mL