Investigating multifaceted action of ibuprofen derivatives towards cox isozymes and interleukin-6 (IL-6) site correlating with various target sites

Abstract

The multifaceted action of new ibuprofen analogs has been investigated against inflammation, neurological and pro-inflammation factors. On the basis of ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, molecular docking as well as molecular dynamics simulation, compound 3 was thought to have good anti-inflammatory activity. As the presence of structural interactions such as conventional hydrogen bonds and electrostatic interactions through the nitrogen atoms of the linker in compound 3 gave strong evidence of its potency. The major finding of the current work is that the presence of appropriate number of hetero atoms (NH, OH) in a compound makes it more efficient than the number of labile groups (i.e., hydroxyl groups). Additionally, the position of hetero atoms in a compound and orientation also play a vital role in its efficacy. It was also screened for in vitro anti-inflammatory activity by membrane stability method, where it has shown 90.8% protection of RBC hemolysis. Thus, compound 3 with effective structural features may have good anti-inflammatory activity.

Communicated by Ramaswamy H. Sarma

Keywords:

• Computational studies
• Synthesis
• Structural features toward various target sites
• Compound 3
• anti-inflammatory activity in vitro

Acknowledgements

Mandeep Kaur and Amandeep Kaur are appreciative to the Council of Scientific and Industrial Research, New Delhi, India, for providing the funding to complete the Ph.D. work with award number 09/140(0179)/2020-EMR-I and 09/0140(13153/2022-EMR-I respectively. We are incredibly grateful to Panjab University, Chandigarh’s superior instrumentation centre, for capturing NMR and HRMS spectra. We are also highly thankful to Dr. Siddalingeshwar K G, Quality Manager, Head -R & D of Scientific & Industrial Research Centre, Bangalore for in vitro anti-inflammatory activity.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Council of Scientific and Industrial Research, India.