Anti-inflammatory and antinociceptive effects of a novel 1,5-benzodiazepine derivative in murine models

This study evaluated the anti-inflammatory and analgesic potential of a novel 1,5-benzodiazepine derivative (MAL) using in vivo models and in silico molecular docking analysis. A total of 264 adult male Swiss albino mice were used for standard pharmacological investigations. MAL was administered at doses of 5, 10, 25, and 50 mg/kg. Diazepam (DZP), diclofenac, and acetaminophen (APAP) were used as reference drugs. Anti-inflammatory activity was assessed using carrageenan-induced paw edema, the air pouch model, and Evans blue-induced vascular permeability. Histopathological analysis was performed to evaluate tissue edema, leukocyte, and neutrophil infiltration. Analgesic effects were evaluated using tail-flick, hot plate, and acetic acid-induced writhing assays. Molecular docking studies were conducted to predict binding interactions of MAL with the α1A-adrenergic receptor (8THL) and COX-2 (3LN1), with results expressed as mean ± SEM. MAL significantly reduced paw edema, with maximal inhibition at 25 mg/kg (43.41% ± 4.23), compared with diclofenac (37.93% ± 3.67). Peak inhibition at 4 h reached 78.54% ± 0.43 for MAL, while 70.14% ± 0.22 for diclofenac. MAL markedly decreased leukocyte and neutrophil infiltration, vascular permeability (66.39% ± 4.18 vs 53.40% ± 4.40), and neutrophil migration in the air pouch, confirmed by histology. Analgesic activity was significant and comparable to standard drugs, supporting both central and peripheral mechanisms. Docking analysis revealed strong binding affinities (- 8.9 and - 8.5 kcal/mol), exceeding reference drugs. MAL exhibits potent anti-inflammatory and analgesic properties, particularly at 25 mg/kg, reducing neutrophil-mediated inflammation, and represents a promising candidate for further pharmacological development.