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, 13 C 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 PGE 2 -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 (LD 50 1000 mg/Kg) and significantly inhibited carrageenan- and PGE 2 -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.

Comprehensive Biological, Photodegradation, Density Functional Theory, and Docking Exploration of Zn(II) and Mn(II) complexes of Piroxicam

“…Metal complexes were synthesized according to the previously published studies. [53,54] The synthesized complexes were put forward for initial characterization by UV analysis through an Ultra-3000 Rittun instrument taking DMSO as a blank. Fouriertransform infrared (FTIR) spectroscopy was performed for acquiring information about changes in functional groups in ligands to synthesize metal complexes on Agilent Technologies Carry 630 FTIR.…”

“…Histamine-induced anti-inflammatory activity was performed by adopting previously published protocol. [54,66] Briefly, rats were randomly divided into four groups (n = 5); Histamine, Mn-Complex, Zn-Complex, and Piroxicam groups. Rats were treated with tested drugs (10 mg/Kg) while rats in histamine (Shanghal Macklin Biochemical Co., Ltd, China) (1 %, 0.1 mL) group were administered with CMC only.…”

“…Metal complexes were synthesized according to the previously published studies [53,54] . The synthesized complexes were put forward for initial characterization by UV analysis through an Ultra‐3000 Rittun instrument taking DMSO as a blank.…”

“…Histamine‐induced anti‐inflammatory activity was performed by adopting previously published protocol [54,66] . Briefly, rats were randomly divided into four groups (n=5); Histamine, Mn‐Complex, Zn‐Complex, and Piroxicam groups.…”

Computational investigation of pyrazinamide drugs and its transition metal complexes using a DFT approach

“…Metal complexes have been widely used in medicinal chemistry due to the enhanced activity they exhibited. [11][12][13][14][15][16] Despite notable advancements in modern chemotherapy, there is still a demand for novel anti-TB agents which are capable of combating drug resistance against Mycobacterium tuberculosis with reduced toxicity and improved potency. 17 Synthesis of transition metal complexes to bring novel drugs over the counter and improving drug delivery is a hot topic for scientists since the last 2 decades as these complexes have proved to be very effective in eradicating diseases with reduced toxicity.…”