DESIGN, SYNTHESIS AND EVALUATION OF ANTITUBERCULAR ACTIVITY OF AMINO AZETIDINONES FROM ISONIAZID
AbstractAzetidin-2-one analogues are reported to exhibit various pharmacological activities like cholesterol absorption inhibitory activity, human tryptase, thrombin and chymase inhibitory activity, vasopressin V1a antagonist activity, antidiabetic, anti-inflammatory, antiparkinsonian and anti-HIV activity in addition to antimicrobial.1-6 In the present study, Isoniazid (INH), the established antitubercular drug was selected as the lead for the design and development of antitubercular agents with minimal toxic effects. A novel series of amino azetidinones were designed from corresponding azetidin-2-ones using various in silico methods. Docking studies were performed at Mtb enoyl acp reductase (4DRE) and the derivatives exhibited best docking scores were prepared from corresponding azetidin-2-ones by treating with various molecules containing amino groups in the presence of TEA. Azetidin-2-ones in turn were obtained from a series of INH Schiff bases by reaction with chloro acetyl chloride. Structures of the newly synthesized compounds were assigned on the basis of elemental analysis, IR, 1H NMR, 13CNMR and mass spectral studies. The newly synthesized compounds were screened for their in vitro antitubercular activity using Alamar blue assay method and the hepatotoxicity was determined by MTT assay method using chang liver cells. AAZ1V, the amino azetidinone obtained from N-[3-chloro-2-(4-chlorophenyl)-4-oxoazetidin-1-yl] pyridine-4-carboxamide (AZ1V) by combining with 4- amino 1, 2, 4-triazole produced significant antitubercular activity. The percentage viability produced by AAZ1V against Chang liver cells for hepatotoxicity was better than the percentage viability produced by INH
Article Information
8
2795-04
607
1605
English
IJPSR
Beena Thomas *and Jyoti Harindran
Department of Pharmaceutical Sciences, Regional Institute of Medical Science and Research, Mahatma Gandhi University, Kottayam, Kerala, India
beenakku@gmail.com
04 February, 2016
28 March, 2016
13 April, 2016
10.13040/IJPSR.0975-8232.7(7).2795-04
01 July, 2016