DESIGNING, SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL PYRIDAZINONE DERIVATIVES Download PDF

The designing and synthesis of selected 6-(4-methylphenyl)-4,5-dihydropyridazin-3(2H)-one, 6-(4-benzylphenyl)-4,5-dihydropyridazin-3(2H)-one and 6-(4-phenoxyphenyl)-4,5-dihydropyridazin-3(2H)-one derivatives was carried out starting from succinic anhydride and aroylpropionic acids using substituted phenylhydrazines guide by computational approach. Estimation of pharmacotherapeutic potential, possible molecular mechanism of action, toxic/side effects and interaction with drug-metabolizing enzymes was also achieved by computational & suitable in-vitro studies. The in-silico docking results showed that compound no. III l & III c were best with analgesic potential while III u & III l were found to be best for anti-inflammatory activity. The results of in-vivo anti-inflammatory studies by carrageenan induced rat paw edema method also revealed that the compound no. III u showed maximum inhibition in paw edema volume followed by compound no. III l while the compound no. III l showed maximum analgesic effect determined by Acetic acid induced writhing method and inhibited the wriths to 69.99 % followed by the compound no. III c. The compound no. III l also showed good analgesic effect determined by Tail immersion method and increased the reaction time to 90 minutes followed by the compound no. III c. In in-vitro anti-bacterial studies, compound no. III j was found to be most effective against Gram positive strain S. aureus and B. cereus showing the maximum zone of inhibition of 32 mm and 33 mm, respectively whereas compound no. III n was found to be most effective against Gram negative strain E. coli and S. flexveri showing maximum zone of inhibition of 29 mm and 30 mm respectively. The compound no. III u was found to have maximum anti-oxidant potential i.e. 89.393 % at concentrations of 1000, 500 and 250 μg/ml. From above results, it is concluded that compound III u has maximum anti-inflammatory and anti-oxidant potential followed by III l. Also anti-oxidant activity has a parallel association with inflammatory process and can be regarded base for anti-inflammatory activity. So, in-vitro results along with in-silico findings strengthens the research findings of these studies.