Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, King Salman International University (KSIU), South Sinai, Egypt.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2250575. doi: 10.1080/14756366.2023.2250575.
In this study, new benzothiazole-pyrimidine hybrids (-, , -, and -) were designed and synthesised. Two different functionalities on the pyrimidine moiety of lead compound were subjected to a variety of chemical changes with the goal of creating various functionalities and cyclisation to further elucidate the target structures. The potency of the new molecules was tested against different tuberculosis (TB) strains. The results indicated that compounds , , , and (MIC = 0.24-0.98 µg/mL) are highly active against the first-line drug-sensitive strain of (ATCC 25177). Thereafter, the anti-tubercular activity was evaluated against the two drug-resistant TB strains; ATCC 35822 and RCMB 2674, where, many compounds exhibited good activity with MIC = 0.98-62.5 3 µg/mL and 3.9-62.5 µg/mL, respectively. Compounds and having the highest anti-tubercular efficiency towards sensitive strain, displayed the best activity for the resistant strains by showing the MIC = 0.98 and 1.95 µg/mL for MDR TB, and showing the MIC = 3.9 and 7.81 µg/mL for XDR TB, consecutively. Finally, molecular docking studies were performed for the two most active compounds and to explore their enzymatic inhibitory activities.
在这项研究中，设计并合成了新的苯并噻唑-嘧啶杂合体（-、-、-和-）。先导化合物嘧啶部分的两个不同官能团经历了多种化学变化，目的是创造各种官能团和环化，以进一步阐明目标结构。新分子的活性针对不同的结核分枝杆菌（TB）菌株进行了测试。结果表明，化合物-、-、-和-（MIC = 0.24-0.98 µg/mL）对一线药物敏感株（ATCC 25177）具有高度活性。随后，对两种耐药结核分枝杆菌菌株（ATCC 35822 和 RCMB 2674）进行了抗结核活性评估，其中许多化合物表现出良好的活性，MIC = 0.98-62.5 3 µg/mL 和 3.9-62.5 µg/mL。化合物-和-对敏感株具有最高的抗结核效率，对耐药株表现出最佳的活性，对 MDR-TB 的 MIC 分别为 0.98 和 1.95 µg/mL，对 XDR-TB 的 MIC 分别为 3.9 和 7.81 µg/mL。最后，对两种最活跃的化合物-和-进行了分子对接研究，以探索它们的酶抑制活性。
