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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.

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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.

New Findings What is the central question of this study?What is the mechanism of wheat‐induced pulmonary inflammation and how does a hydrazide derivative modulate it? What is the main finding and its importance?A hydrazide derivative significantly reduced wheat‐induced pulmonary inflammation in a rat model mainly by down‐regulating inflammatory cell infiltration, pathological lesions in the lungs and the level of pro‐inflammatory cytokines, COX‐1, COX‐2 and T‐cell proliferation. Abstract We investigated the ameliorative anti‐inflammatory effect of a previously synthesized hydrazide derivative (N′‐(4‐methoxybenzylidene)‐6‐(4‐chlorophenyl)‐3‐methyl‐1‐phenyl‐1H‐pyrazolo[3,4‐b]pyridine‐4‐carbohydrazide; MD) as an immunomodulator in a newly developed allergen‐induced pulmonary inflammation (AIPI) rat model. Wheat and thresher dust were used as allergens to induce pulmonary inflammation while MD was used to reverse the inflammatory response. Blood and bronchoalveolar lavage fluid (BALF) were collected after killing the rats and inflammatory cells were counted. Histological analysis of lung airways was carried out by haematoxylin and eosin and periodic acid–Schiff staining while the level of total serum IgE, interleukin (IL)‐4, IL‐5 and cyclooxygenase (COX)‐1 in BALF and in vitro T‐cell proliferation in spleen were measured through enzyme‐linked immunosorbent assay. mRNA expression level of IL‐4, IL‐5, IL‐13, transforming growth factor β (TGF‐β), interferon‐γ, tumour necrosis factor α, COX‐1 and COX‐2 was evaluated by qRT‐PCR. A liver and kidney function test was used to observe any toxic impact of MD. The results indicated that 2 mg of wheat and thresher dust led to higher levels of inflammatory cytokines in the blood, BALF and lung airways of rats. MD potentially down‐regulated the inflammatory cell infiltration in BALF and pathological lesions in the lung airways of AIPI rats. MD significantly suppressed the elevated total serum IgE, along with IL‐4, IL‐5, IL‐13, TGF‐β, COX‐1 and COX‐2 mRNA expression and T‐cell proliferation in spleen. In conclusion, MD at 10 mg kg−1 exhibited a significant reduction in all the markers in both wheat‐ and thresher dust‐induced pulmonary inflammation mainly by inhibiting pro‐inflammatory cytokine production and T‐cell proliferation. The data suggest that inhibition of the T‐cell response may be responsible for the modulative effect of MD in an AIPI rat model.