Isoxazole analogues of dibenzazepine as possible leads against ulcers and skin disease: In vitro and in silico exploration

• DOI: 10.1016/j.jsps.2023.101877
• Publication Date: 2023-11-16T22:44:57Z
• Authors: Majid Khan; Sobia Ahsan Halim; Luqman Shah; Ajmal Khan; Izzaddinn E. Ahmed; Ashraf N. Abdalla; Afnan Jan; Asaad Khalid; Abida Mushtaque; Ahmed Al-Harrasi
• Keywords: Isoxazole; IC50; Docking (animal)

Utilizing multi-target drugs shows great promise as an effective strategy against polygenic diseases characterized by intricate patho-mechanisms, such ulcers, skin dermatitis, and cancers. The current research centers around the creation of hybrid compounds, connecting dibenzazepine isoxazole, with aim exploring their potential inhibitors for urease tyrosinase enzymes. Analogs 6a, 6b, 6d, 6 h-6j, l demonstrated strong inhibitory enzyme IC50 values 4.32 ± 0.31-12.36 0.48. Whereas analogs 6c, 6e, 6f, 6h-6m, 6r exhibited potent activities 3.67 0.91-15.60 0.18 μM. Furthermore, compounds 6i, 6n, showed weak toxic effect in BJ-cell line, whereas remaining were found non-toxic to normal cell line. mechanistic studies both enzymes competitive mode inhibition. Molecular docking was employed establish relationship between structure activity elucidate interaction mechanism. This analysis revealed that active crucial interactions site residues tyrosinase, thus corroborating our experimental results. Hence, generated derivatives dibenzazepine-linked isoxazoles present intriguing starting points further investigations into future modification enhancement.