Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman, Jordan.
Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):869-884. doi: 10.1080/14756366.2021.1900162.
The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstituted-1,2,4-oxadiazole derivatives () were tested against H37Rv, MDR and XDR strains of MTB. Of which, compound with para-trifluorophenyl substituted oxadiazole showed excellent activity against the susceptible H37Rv and MDR-MTB strain with a MIC values of 8 and 16 µg/ml, respectively.To understand the mechanism of action of these compounds () and identify their putative drug target, molecular docking and dynamics studies were employed against a panel of 20 mycobacterial enzymes reported to be essential for mycobacterial growth and survival. These computational studies revealed polyketide synthase (Pks13) enzyme as the putative target. Moreover, ADMET predictions showed satisfactory properties for these compounds, collectively, making them, particularly compound , promising leads worthy of further optimisation.
（MTB）中多药耐药和广泛耐药（MDR 和 XDR）菌株的惊人增长，促使科学界寻找新型、有效和更安全的治疗方法。为此，一系列 3,5-二取代-1,2,4-噁二唑衍生物（）对 H37Rv、MDR 和 XDR 株 MTB 进行了测试。其中，带有对三氟苯基取代噁二唑的化合物表现出对敏感 H37Rv 和 MDR-MTB 菌株的优异活性，MIC 值分别为 8 和 16μg/ml。为了了解这些化合物（）的作用机制并确定它们的潜在药物靶标，针对 20 种据报道对分枝杆菌生长和存活至关重要的分枝杆菌酶进行了分子对接和动力学研究。这些计算研究表明聚酮合酶（Pks13）酶是潜在的靶标。此外，ADMET 预测表明这些化合物具有令人满意的性质，总的来说，它们使化合物成为具有进一步优化价值的有前途的先导化合物。
