Synthesis and Biologic Evaluation of Substituted 5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one Derivatives as Selective COX‐2 Inhibitors: Molecular Docking Study

Abstract

The present study reported the synthesis and biologic evaluation of new pyrazolone derivatives for COX-2 inhibitory activities and investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw edema model as well as in vitro using HRBC membrane stabilization and protein denaturation method. Eight derivatives showed pronounced COX-2 inhibition, and 5a, 5d, and 5f exhibited the highest COX-2 inhibition. The derivatives were further evaluated for antioxidant activity wherein 5a and 5b showed potent free radical-scavenging activity against DPPH, nitric oxide, and hydrogen peroxide radicals. Molecular docking study revealed the binding orientations of pyrazolone derivatives into the active sites of COX-2 and thereby helps to design the potent inhibitors.

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

“…A series of 5-methyl-2-phenyl-1H-pyrazol-3 (2H)-one analogues were prepared and determined for their anti-inflammatory effects [96]. The outcome showed that the derivatives 130 and 131 (Fig.…”

3-Methyl-4-substituted Benzylidene Pyrazol-5-ones: Synthesis, Evaluation of Antinociceptive Activities and in silico Studies

“…Binding modes of the studied pyrazolones were found to be similar to that of celecoxib and most of them were found to interact with Phe-504 amino acid residue. Pyrazolones possessing phenylurea or phenylthiourea, interact with different amino acid residues (π-π stacking of phenyl ring with Trp-387 and Tyr-385) indicating that pyrazolones affinity for COX-2 enzyme is influenced/effected with substitution [27].…”

“…2. TRPV1 ion channel: TRPV1or vanilloid receptor 1 can be activated by eicosanoids, capsaicin, protons and resiniferatoxin [27]. It is expressed by primary afferent sensory neurons of the pain pathway and plays pivotal role in nociception and neurogenic inflammation [30][31][32].…”

Synthesis and Cytotoxic Evaluation of Some Substituted 5-Pyrazolones and Their Urea Derivatives

“…Some of their pharmacological uses include analgesic, anti-inflammatory, antipyretic, antiparasitic, antimalarial, and antifungal effects [5]. Some 5-pyrazolones inhibit enzyme activity that causes neurodegenerative effects [6], and others are used as sedatives. In agricultural industries, they are used as pesticides against insects and weeds [7,8].…”