In this study, we present novel pyrazine-1,3,4-oxadiazole hybrids (T1-T9) and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivatives (T10-T18), which possess remarkable antimicrobial activity. These compounds have been meticulously scrutinized for their efficacy in combatting the M. tuberculosis H37Rv strain. Three compounds T7, T8, and T17 showed promising antitubercular activity with MIC of 1.56 µg/mL. The target compounds are also evaluated for their antibacterial activity against S. aureus, S. mutans, E. coli, and S. Typhi, and antifungal activity against A. niger. Most of the compounds showed significant antibacterial and antifungal activity. All the active compounds exhibited very low toxicity and none of the active compounds were toxic to the normal cells. To deepen our understanding of these compounds, an in-silico ADME, and molecular docking analysis against the DprE1 enzyme were conducted, followed by DFT studies to shed some light on their electronic properties, and enhance our grasp of their pharmacological potential.

中文翻译：

---

新型吡嗪-1,3,4-噁二唑/[1,2,4] 三唑并[3,4-b][1,3,4]噻二嗪杂交体作为强效抗分枝杆菌剂的设计、合成、表征和生物学评价


在这项研究中，我们提出了新型吡嗪-1,3,4-噁二唑杂交体 （T1-T9） 和 [1,2,4] 三唑并[3,4-b][1,3,4]噻二嗪衍生物 （T10-T18），它们具有显着的抗菌活性。这些化合物在对抗结核分枝杆菌 H37Rv 菌株方面的功效已经过仔细审查。3 种化合物 T7 、 T8 和 T17 显示出良好的抗结核活性，MIC 为 1.56 μg/mL。还评估了目标化合物对金黄色葡萄球菌、变异链球菌、大肠杆菌和伤寒沙门氏菌的抗菌活性，以及对黑曲霉菌的抗真菌活性。大多数化合物显示出显着的抗菌和抗真菌活性。所有活性化合物均表现出非常低的毒性，并且没有一种活性化合物对正常细胞有毒。为了加深我们对这些化合物的理解，我们针对 DprE1 酶进行了计算机模拟 ADME 和分子对接分析，然后进行了 DFT 研究，以阐明它们的电子特性，并增强我们对它们药理潜力的把握。