Meloxicam Inhibited the Glycation Phenomenon via Scavenging Di-Carbonyl Moieties

Talha bin Fayyaz; Ghulam Abbas; Hammad Ahmed; Najeeb Khatian; Shumaila Usman; Uzair Nisar; Noor Ul Ain; Mohammad Abid; Syed Abid Ali

doi:10.1590/s2175-97902026e24799

Authors

Talha bin Fayyaz Ziauddin University , Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi
Ghulam Abbas Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi-75600 , Ziauddin University
Hammad Ahmed Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi , Ziauddin University
Najeeb Khatian Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi , Ziauddin University
Shumaila Usman Department of Molecular Medicine, Ziauddin University, Karachi , Ziauddin University
Uzair Nisar Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University, Karachi , Ziauddin University
Noor Ul Ain Department of Pharmacology, Institute of Pharmaceutical Sciences, Jinnah Sindh Medical University, Karachi , Jinnah Sindh Medical University
Mohammad Abid H.E.J. Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi , University of Karachi
Syed Abid Ali H.E.J. Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi , University of Karachi

DOI:

https://doi.org/10.1590/s2175-97902026e24799

Keywords:

Glycation, Meloxicam, Carbonyl entrapping, Fructose, BSA

Abstract

Senescence or aging is often associated with onset of morbidities, which have been attributed to theharmful phenomenon of glycation. To date, no drug is available to combat this deleterious process.The drug repurposing is a robust and cost-effective approach to identify potential candidate moleculesfor drug discovery programs. In present study, Meloxicam (MEL) was evaluated for its capacity to berepurposed against glycation. Using the Fructose-BSA model, the anti-glycation effect was evaluatedby measuring intrinsic fluorescence of Advanced Glycation End Products (AGEs). The fructoseamineload and free lysine availability was estimated using NBT and TNBSA assays respectively. The BSAsecondary structure was assessed by Thioflavin-T, Congo red and Circular Dichroism tests. Finally, lysine blockade and carbonyl entrapment was evaluated as a possible mode of anti-glycation action.Our data showed that MEL (0.5, 1, and 2mM) has significantly reduced the AGEs formation (IC₅₀ = 0.25mM). The load of fructosamine adducts along with free lysine availability was found to be reduced.The secondary structure of BSA was preserved. Regarding mode of action, MEL did not block lysineresidues, which was also supported by computational data. However, it was found to entrap carbonylintermediates. In conclusion, the present study demonstrate that MEL possess anti-glycation potential, which can be attributed to entrapment of carbonyl intermediates. Hence, MEL, a clinically used NSAIDs, present itself as promising candidate to be repurposed against deleterious phenomenon of glycation.

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Meloxicam Inhibited the Glycation Phenomenon via Scavenging Di-Carbonyl Moieties

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