Synthesis, Spectroscopic and Biological Investigation of a New Ca(II) Complex of Meloxicam as Potential COX-2 Inhibitor.

Abstract

Drug development on basis of coordination compounds provides versatile structural and functional properties as compared to other organic compounds. In the present study, a new Ca(II) complex of meloxicam was synthesized and characterized by elemental analysis, FT-IR, UV–Vis, 13C NMR, SEM–EDX, powder XRD and thermal analysis (TGA). The Ca(II) complex was investigated for its in vitro, in vivo biological activities and in silico docking analysis against COX-1 and COX-2. The spectral analysis indicates that the meloxicam acts as a deprotonated bidentate ligand (coordinated to the metal atom through the amide oxygen and the nitrogen atom of the thiazolyl ring) in the complex. SEM–EDX and powder XRD analysis depicted crystalline morphology of Ca(II) complex with a crystalline size of 32.86 nm. The in vitro biological activities were evaluated by five different antioxidant methods and COX inhibition assay, while in vivo activities were evaluated by carrageenan-, histamine- and PGE2-induced paw edema methods and acetic acid-induced writhing test. The Ca(II) complex showed prominent antioxidant activities and was found to be more selective toward COX-2 (43.77) than COX-1 as compared to meloxicam. It exhibited lower toxicity (LD50 1000 mg/Kg) and significantly inhibited carrageenan- and PGE2-induced inflammation at 10 mg/Kg (P < 0.05), but no significant effect was observed on histamine-induced inflammation. Moreover, Ca(II) complex significantly reduced the number of writhes induced by acetic acid (P < 0.05). The in silico molecular docking data revealed that Ca(II) complex obstructed COX-2 (dock score 6438) more effectively than COX-1 (dock score 5732) as compared to meloxicam alone.