Abstract
Present research was designed to synthesize and characterize the flurbiprofen derivatives and to evaluate their analgesic, anti-inflammatory and gastro-protective activities in post-operative and chronic inflammatory pain models. Flurbiprofen derivatives were produced by using three-step processes involving esterification, hydrazide production, and schiff base, each of which modified a different carboxyl group. All the newly synthesized flurbiprofen derivatives (NS5-NS8) were characterized by 1H NMR,13C NMR,19F NMR and HR-ESI-MS, and the post-operative, inflammatory pain and ulcerogenic activities were determined in well-established in-vivo animal models. To evaluate post-operative and inflammatory pain, various doses of compounds [1, 3, 10, and 30 mg/kg (bwt)] were used, while their ulcerogenic potential was assessed at doses of 100 and 150 mg/kg (bwt). The incisional damage linked pain was significantly (p < 0.001) reduced by derivatives at different doses in both the acute and repeated tests with decreased response of phologistic agent-induced inflammation. The stomach histology and biochemical features demonstrate that the synthesized derivatives have no potential to cause ulcerogenicity as compared to aspirin and flurbiprofen. Furthermore, docking shows that the hydrazide moiety of these compounds is crucial in interacting within COX-2 binding site. Therefore, the synthesized compounds exhibit strong analgesic and anti-inflammatory effects and a low risk of causing ulcers. These attributes render them potentially valuable therapeutic agents for the treatment of pathological disorders associated with inflammation and pain.
Communicated by Ramaswamy H. Sarma
Acknowledgements
The author would like to thanks to University of Nizwa for general support of this work. The authors extend their appreciation to the Deputyship for Research and innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number (ISP23-81).
Disclosure statement
No potential conflict of interest was reported by the author(s).
Ethics approval
All animal procedures were approved by the Departmental Animal Ethical Committee, University of Malakand, KPK, and Pakistan (DAEC/PHARM/2015/16) and were conducted according to the UK animal scientific procedure act, 1986.
Author’s contribution
Conceptualization, N.K., A.K. and A.A-H.; methodology, N.Z.S. N.U.I. and M.K. software, S.A.H.; formal analysis, I.K. and H.K.; investigation, H.A.A. and M.K. resources, N.K., A.K. and A.A-H.; data curation, A.N.A. and A.K. writing—original draft preparation, N.Z.S. and N.K.; writing—review and editing, S.A.H., A.K. and Asaad K. visualization, H.A.A. and S.A.H.; supervision, N.K., A.K. and A.A-H.; funding acquisition A.K. A.N.A., Asaad K. and A.A-H.