Synthesis and Biological Evaluation of Novel 2-(4-acetyl-3-methyl- 5-(arylamino) thiophen-2-yl)-3-arylquinazolin-4(3H)-one Derivatives as Potential Anti-inflammatory and Antioxidant Agents

Abstract

Background: A new series of 2-(4-acetyl-3-methyl-5-(arylamino) thiophen-2- yl)-3-arylquinazolin-4(3H)-one derivatives (11a-11j) were synthesized from acetyl acetone, phenyl isothiocyanate and 2-chloromethyl quinazolinone.

Objective: Due to side effects of Non Steroidal Anti-Inflammatory Drugs (NSAID), an attempt was made to identify the novel tetrasubstituted thiophene lead compound as potential anti-inflammatory and antioxidant agent.

Methods: Then newly synthesized compounds were characterized by IR spectroscopy, 1H NMR and mass spectrometry. The synthesized compounds were screened for their in vivo anti-inflammatory activity in carrageenan-induced rat hind paw edema model at dose 20mg/kg body weight using diclofenac sodium as a standard drug. The compounds were also evaluated for their in vitro DPPH free radical-scavenging activity and nitric oxide radical scavenging activity at the concentrations of 10, 20, 40, 60, 80 and 100 µg/mL using ascorbic acid as standard drug.

Results: The results from carrageenan-induced rat hind paw edema showed that compounds 11e, 11f and 11b show a significant anti-inflammatory activity of 46.61%, 48.94% and 47.04 % protection respectively to inflamed paw but less than diclofenac sodium. Compounds 11h and 11e show good DPPH free radical scavenging and nitric oxide radical scavenging activity, respectively.

Conclusion: From results, it was observed that highly substituted thiophene scaffold exhibits anti-inflammatory and antioxidant activity.

Keywords: Anti-inflammatory activity; COX; PGs; antioxidant activity; inflammation; tetrasubstituted thiophene..