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

Abstract

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.

Rational Design, Synthesis and Biological Evaluation of Novel Pyrazoline-Based Antiproliferative Agents in MCF-7 Cancer Cells

“…First, the 3-(4-aryl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-ones 2a – c were obtained through the Claisen–Schmidt reaction [ 53 ] by direct condensation of aromatic aldehydes 1a–c with dimethoxy acetophenone in the presence of sodium hydroxide [ 54 , 55 , 56 ]. This step was followed by the reaction of compounds 2a – c with thiosemicarbazide under a basic condition to give 3-(3,4-dimethoxyphenyl)-5-(4-aryl)-4,5-dihydro-1 H -pyrazole-1-carbothioamides 3a – c , respectively ( Chart 1 ) [ 57 , 58 ]. This reaction proceeded through a condensation reaction followed by subsequent cyclization via Michael addition reaction.…”

Synthesis and biological evaluation of benzamide‐chalcone hybrids as potential c‐Met kinase and COX‐2 inhibitors

“…Molecular docking studies for the COX‐2 (PDB 5KIR and 3LN1) and COX‐1 (PDB 3K66) enzymes. [ 69 ] The structures were prepared using the protein preparation wizard in Maestro 11.1, Schrodinger 2017‐1. [ 66 ] Only chain A was retained and all cofactors, water molecules, and other molecules which were not contributing toward any interactions were removed.…”