Vol. 5, Issue 10 (2016)

Author(s):
Beena Thomas, Jyoti Harindran and KS Devaky

Abstract:
Two novel series of derivatives of isoniazid, the well-established antitubercular drug were designed with the aim of developing an antitubercular agent with better anti-inflammatory activity. Schiff bases of isoniazid were prepared by the treatment of isoniazid with various aldehydes. These Schiff bases on treatment with chloroacetyl chloride produced azetidinones, which on further treatment with different amines resulted in the first series of compounds, the amino azetidinones. The second series of derivatives were obtained by the conversion of isoniazid Schiff bases to thiazolidinones by treatment with thioglycolic acid followed by conversion to corresponding Mannich bases by treatment of the thiazolidinones with various secondary amines. Both series of derivatives were designed using in silico studies. Docking studies for anti-inflammatory activity were performed using cyclooxygenase-2(PDB ID: ICX2). Structures of the newly synthesized compounds were assigned on the basis of elemental analysis and various spectroscopic techniques like IR, ¹H NMR, ¹³CNMR and mass analysis. The derivatives with best docking scores from each group were screened for anti-inflammatory activity by carrageenan induced paw edema method. The study performed using the compounds N-[2-(4-chlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]pyridine-4-carboxamide (TZ1V), N-{2-(4-chlorophenyl)-5-[(dimethylamino)methyl]-4-oxo-1,3-thiazolidin-3-yl}pyridine-4-carboxamide (MB1V-2) and N-[2-(4-chlorophenyl)-3-(methylamino)-4-oxoazetidin-1-yl]pyridine-4-carboxamide (AAZ1) as representatives from each group were found to be significantly reducing edema formation at a dose level of 100 mg/kg.