Synthesis, spectroscopic, in vitro, in vivo biological evaluation, and in silico docking analysis of new meloxicam metal complexes

Abstract

In the present study, two new meloxicam complexes with Mg(II) and Sr(II) were synthesized and characterized by spectroscopic and analytical methods, that is, UV–vis, IR, 1H NMR, 13C NMR, powder XRD, SEM–EDX, and TG analysis. The biological evaluation was done by in vitro antioxidant, BSA‐binding, DNA cleavage activities, and in vivo anti‐inflammatory, analgesic, and anxiolytic methods. Furthermore, in silico docking was done with Keap1 receptor to visualize the anti‐inflammatory effect of complexes. The spectral characterization suggested that meloxicam coordinated with the metal ions by oxygen and nitrogen of amide group and thiazolyl ring (Oamide and Nthiazolyl), respectively. The SEM pictures depicted dissimilar morphologies, and the powder XRD patterns showed different crystallinities of complexes than meloxicam. TG analysis exhibited high thermal stabilities of complexes and Coats–Redfern method was employed to calculate the important thermodynamic parameters. The complexes showed effective biological activities and enhanced safety index (LD50 = 1000 mg kg−1). The Mg(II) complex revealed greatest inhibitory effects in carrageenan‐induced paw inflammation (92.85%) and in acetic acid‐induced writhing (71.05%). Furthermore, the complexes showed higher potential to bind with BSA and cleave the DNA as compared with the meloxicam. Moreover, molecular docking against Keap1 showed that Mg(II) complex inhibited Keap1 with highest docking score (6166 kcal mol−1), docking area (804.40) and ACE (−417.49 kJ mol−1) which explained its higher anti‐inflammatory effect. Mg(II) complex of meloxicam might be considered as a candidate anti‐inflammatory drug; however, more research is required to investigate their other biological potential.