Comparative physicochemical, anti-inflammatory, and analgesic activity assay of synthesized chromium and nickel complexes of indomethacin

Abstract

Objectives: Complexation of non-steroidal anti-inflammatory drugs (NSAIDs) with transition metals—chromium and nickel is a unique approach of masking the inherent side effect of gastrointestinal hemorrhage and ulceration of NSAID along with imparting beneficial pharmacological effects. Methods: Chromium and nickel complexes of indomethacin were synthesized followed by characterization of these complexes by FT-IR spectroscopy, UV–Visible spectroscopy, atomic absorption spectroscopy, calorimetric DSC analysis, and melting point analysis. For screening of biological activities to uncover potentially interesting pharmacological properties, the metal complexes were assayed for peripheral analgesic, central analgesic, and anti-inflammatory activity. Results: Nickel-indomethacin complex at dose of 20 mg/kg showed peripheral analgesia of 67.03% by inhibiting writhing and at its dose of 20 mg/kg showed potent central analgesic action at 60 min (92% elongation of tail flicking time). In anti-inflammatory study, nickel-indomethacin and chromium indomethacin complex at its 15 mg/kg dose in the 2 h showed inhibition of paw edema of 78.35 and 73.23%, respectively, which is comparable to the standard indomethacin. Conclusion: Based upon the results, it can be predicted that chromium and nickel complex of indomethacin may show promising pharmacological effects which can be revealed by extensive analysis using pharmacokinetic and pharmacodynamic test model.

Keywords:

• nickel-indomethacin
• chromium-indomethacin
• FT-IR
• UV-visible
• DSC analysis
• peripheral analgesic
• central analgesic
• anti-inflammatory activity

Public Interest Statement

Non-steroidal Anti-Inflammatory drugs, commonly known to people as pain killers are some of the most widely used medications. However, they usually come with some severe side effects namely ulceration and possibly perforation in stomach and small intestine, which can limit the use of these medications.

In this report, we showed that if these medicines are combined with metals, then their efficacy remains the same or increases. At the same time, the above-mentioned side effects would also diminish in severity.

Acknowledgments

We are grateful to the Department of Clinical Pharmacy and Pharmacology, University of Dhaka.

Additional information

Notes on contributors

Abhijit Sukul

Our research group comprises of Abhijit Sukul, Saikat Kumar Poddar, Shahadat Hossain, Sanjana Haque, Kumar Kulldeep Niloy and led by Sajal Kumar Saha. Since 2013, we have published five papers related to pharmacological and toxicological investigation of transition metal complexes of various NSAIDs. So far, we have investigated complexes of indomethacin, tolfenamic acid, and aceclofenac as well as showed that these complexes may be less toxic and more potent than the parent drug molecules.

In our current report, we have described the synthetic procedure as well as pharmacological activities of chromium and nickel complexes of indomethacin. A simple synthetic procedure for chromium and nickel complexes of indomethacin has been described, which may prove to be valuable to aspiring researchers in this field. Furthermore, we have shown that chromium and nickel complexes are more efficacious than indomethacin alone, which may open a window to further research regarding the mechanism of action and large-scale investigation of these complexes.