Synthesis of some pyrazolyl benzenesulfonamide derivatives as dual anti-inflammatory antimicrobial agents

Abstract

Four series of pyrazolylbenzenesulfonamide derivatives were synthesized and evaluated for their anti-inflammatory activity using cotton pellet induced granuloma and carrageenan-induced rat paw edema bioassays. Moreover, COX-1 and COX-2 inhibitory activity, ulcerogenic effect and acute toxiCIT000y were also determined. Furthermore, the target compounds were screened for their in-vitro antimicrobial activity against Eischerichia coli, Staphylococcus aureus and Candida albicans. Compounds 4-(3-Phenyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9a and 4-(3-Tolyl-4-cyano-1H-pyrazol-1-yl)benzenesulfonamide 9b were not only found to be the most active dual anti-inflammatory antimicrobial agents in the present study with good safety margin and minimal ulcerogenic effect but also exhibited good selective inhibitory activity towards COX-2. A docking pose for 9a and 9b separately in the active site of the human COX-2 enzyme was also obtained. Therefore, these compounds would represent a fruitful matrix for the development of dual anti-inflammatory antimicrobial candidates with remarkable COX-2 selectivity.

Keywords::

• Pyrazole
• anti-inflammatory
• antimicrobial
• ulcerogenic effect
• docking
• acute toxiCIT000y
• cox-2
• inhibitors

Acknowledgements

The authors wish to thank Dr. Elsayed Aboulmagd, Department of Microbiology, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt and Dr. Azza Baraka, department of Pharmacology, Faculty of Pharmacy, University of Alexandria for their assistance during biological testing.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.