SYNTHESIS, CHARACTERIZATION AND ANTITUBERCULAR ACTIVITY OF 6-(ARYL)-2-(SUBSTITUTED METHYL)-4,5-DIHYDRO(2H)PYRIDAZIN-3-ONE DERIVATIVES AGAINST MYCOBACTERIUM TUBERCULOSIS H37RVAbstract
Two series of pyridazinone derivatives, 6-(aryl)-2-(substituted methyl)-4,5-dihydro (2H) pyridazin-3-one derivatives (3a-8a and 3b-8b) were synthesized by reacting 6-phenyl substituted 2,3,4,5-Tetrahydro pyridazin-3-one (2a and 2b) with cyclic secondary amine under Mannich reaction conditions. These final compounds (3a-8a and 3b-8b) were characterized by spectral analysis (IR, 1HNMR and mass spectroscopy) and evaluated for anti-tubercular activities against Mycobacterium tuberculosis H37Rv strain by Microplate Alamar Blue assay (MABA) method. Most of the compounds were showed significant anti-tubercular activity. Compounds (7a and 7b) were showed maximum antitubercular activity with 6.25 μg/ml minimum inhibitory concentration (MIC) value and compounds (4a, 5a, 8a and 3b, 4b, 6b, 8b) were exhibited 12.5 μg/ml MIC value and other remaining compounds (3a, 6a and 5a) were found less potent (12.5 μg/ml) MIC value than the reference drugs when compared with reference drugs [pyrizinamide (3.125 μg/ml)] and (streptomycin 6.25 μg/ml) MIC values. Among the synthesized pyridazinone derivatives, compound (7a and 7b) emerged as a lead compound with good anti-tubercular activity. These biological activities differences mainly depend on the different type of substitutions on the pyridazinone ring system.
M. Asif *, Abida and M. Imran
Department of Pharmaceutical Chemistry, Himalayan Institute of Pharmacy and Research, Dehradun, Uttarakhand, India.
26 April 2019
19 August 2019
01 September 2019
01 February 2020