Investigations of New N¹-Substituted Pyrazoles as Anti-Inflammatory and Analgesic Agents having COX Inhibitory Activity

Abstract

Background: The search is ongoing for ideal anti-inflammatory and analgesic agents with promising potency and reasonable selectivity. Methods: New N¹ -substituted pyrazoles with or without an acetamide linkage were synthesized and evaluated for their anti-inflammatory and analgesic activities. COX inhibitory testing, molecular docking, molecular dynamics simulation and antiproliferative activity assessments were performed. Results: All compounds exhibited anti-inflammatory activity up to 90.40% inhibition. They also exhibited good analgesic activity with up to 100% protection. N¹ -benzensulfonamides 3d, 6c and 6h were preferentially selective agents toward COX-2. Compound 3d showed good cytotoxicity against MCF-7 and HTC116 cancer cell lines. Molecular modeling studies predicted the binding pattern of the most active compounds. Molecular dynamics confirmed the docking results. All compounds showed remarkable pharmacokinetic properties.

Graphical abstract

Keywords::

• analgesic
• anti-inflammatory
• antitumor
• COX-inhibitor
• molecular dynamics
• substituted pyrazole

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.future-science.com/doi/suppl/10.4155/fmc-2023-0302

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.