Engineering Laboratory of Organometallic and Molecular Materials and Environment, Faculty of Sciences Dhar El Mahraz, University Sidi Mohamed Ben Abdellah, P.O. Box 1796, Atlas, Fez 30000, Morocco.
Laboratory of Epidemiology and Research in Health Sciences, Faculty of Medicine, Pharmacy and Dentistry, University Sidi Mohammed Ben Abdellah, Fez 30070, Morocco.
Molecules. 2024 May 26;29(11):2510. doi: 10.3390/molecules29112510.
Novel isoxazole-triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (H NMR and C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely ATCC 25923, ATCC BAA-44, and ATCC 25922 as well as one strain isolated from the hospital environment . The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested ATCC 25922 and pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound proved to have a bactericidal action on the ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate with the proteins of and bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound .
新型异噁唑-三唑缀合物已根据多步合成方法，以 3-甲酰基色酮为起始原料高效合成。目标缀合物和中间产物的结构通过标准光谱技术（1H NMR 和 13C NMR）进行了表征，并通过质谱（MS）进行了确认。对所有合成的化合物进行了抗菌活性筛选，以评估其对三种 ATCC 参考菌株（即 ATCC 25923、ATCC BAA-44 和 ATCC 25922）以及一种从医院环境中分离的菌株的抗菌活性。结果表明，与标准抗生素相比，缀合物 7b 对测试的 ATCC 25922 和 病原菌菌株表现出更强的抗菌反应。此外，杂交化合物 7d 对 ATCC 25922 菌株具有杀菌作用，这可以从 MBC 测定的结果中得到证明。此外，ADMET 药代动力学特征表明，所研究的化合物具有良好的药代动力学特征，口服生物利用度也较高。进行了分子对接和分子动力学模拟，以探索缀合物 7b 与 和 细菌株蛋白的抑制机制和结合能。计算机模拟结果与化合物 7b 的体外评估数据一致。
