Design, Synthesis, Characterization and In Silico Molecular Docking Studies and In Vivo Anti-inflammatory Activity of Pyrazoline Clubbed Thiazolinone Derivatives

Abstract

The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities, including inflammatory action. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure. Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant, etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have a significant anti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate it as an anti-inflammatory agent. In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a threestep reaction. The compounds were subjected to spectral analysis by Infrared, Mass, and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized derivatives were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Compounds PT-1, PT-3, PT-4, and PT-8 exhibited significant anti-inflammatory activity at 3rd hour, being 50.7%, 54.3%, 52.3%, and 57%, respectively, closer to that of the standard drug indomethacin (61.9%). From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed a docking score of -6.5 kJ/mol, compound PT-1 exhibited the highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 had a docking score of 9.4 kJ/mol for COX-2. It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors was very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.