Background:
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. 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 significantanti-inflammatory activity.
The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate
as anti-inflammatory agent.
Method:
In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy
and elemental analysis data. All the synthesized 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.
Results:
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 docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and
compound PT-8 having docking score of 9.4 kJ/mol for COX-2.
Conclusion:
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 were very good. It is concluded that the synthesized
derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.
Computational Structure-Based De Novo Design of Hypothetical Inhibitors against the Anti- Inflammatory Target COX-2
