Alharbi Arwa, Alalawy Adel I, Alsharif Shaker T, Alqahtani Alaa M, Alessa Ali H, Alsahag Mansoor, Alisaac Ali, El-Metwaly Nashwa M
Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah, 24230, Saudi Arabia.
Department of Biochemistry, Faculty of Science, University of Tabuk, Saudi Arabia.
Heliyon. 2024 Oct 2;10(19):e38905. doi: 10.1016/j.heliyon.2024.e38905. eCollection 2024 Oct 15.
A series of benzothiazolopyrimidine-thiazole conjugates , , and were produced through the reactions of 8-acetylbenzothiazolopyrimidine-thiosemicarbazone compound with chloroacetone, (un)substituted phenacyl chlorides, and ethyl chloroacetate, respectively. Based on DFT study, the synthesized conjugates had a twisted shape, except for the parent benzothiazolopyrimidine and its thiosemicarbazone compound , which were flat. The study of FMO's also showed that the substituted thiazole derivatives and have equivalent configurations of HOMO and LUMO, as well as exhibiting the least FMO's gap (ΔE). The antimicrobic activeness of the constructed derivatives has been assessed against the two Gram's types of bacteria and fungi using the broth microdilution method. The benzothiazolopyrimidine-thiazole conjugate exhibited the strongest inhibition towards Gram-negative (MIC <29 μg/mL), while a valuable performance was observed towards (MIC <132 μg/mL). Also, it displayed broad-spectrum activity with the least MIC fungi (<207 μg/mL). In contrast, the conjugate demonstrated selective efficacy against Gram + ve and bacteria (MIC <40 and < 47 μg/mL, respectively). Besides, molecular docking of these benzothiazolopyrimidine derivatives with the PDB: 2XCT protein carried out to discover their binding types, RMSD, binding scores, and interactions pocket for each derivative, including a drug reference. Furthermore, their physicochemical-pharmacokinetic profile has estimated the SwissADME prediction. The data indicated that derivative demonstrated constructive pharmacokinetics (M. Wt. 269.28), lipophilicity (Log Po/w = 1.45), and TPSA = 103.47, which foretold high (GI) absorption and good bioavailability = 0.55 without interrupting Lipinski's rules.
一系列苯并噻唑并嘧啶 - 噻唑共轭物，即化合物1、2和3，分别通过8 - 乙酰基苯并噻唑并嘧啶 - 硫代氨基脲化合物与氯丙酮、（未）取代的苯甲酰氯以及氯乙酸乙酯反应制得。基于密度泛函理论（DFT）研究，除了母体苯并噻唑并嘧啶及其硫代氨基脲化合物为平面结构外，合成的共轭物均呈扭曲形状。前线分子轨道（FMO）的研究还表明，取代的噻唑衍生物2和3具有等效的最高占据分子轨道（HOMO）和最低未占据分子轨道（LUMO）构型，并且展现出最小的FMO能隙（ΔE）。已使用肉汤微量稀释法评估了所构建衍生物对两种革兰氏类型细菌和真菌的抗菌活性。苯并噻唑并嘧啶 - 噻唑共轭物1对革兰氏阴性菌大肠杆菌（MIC <29 μg/mL）表现出最强抑制作用，同时对金黄色葡萄球菌（MIC <132 μg/mL）也观察到有显著效果。此外，它对真菌显示出广谱活性，最低抑菌浓度（MIC）最低（<207 μg/mL）。相比之下，共轭物3对革兰氏阳性菌枯草芽孢杆菌和金黄色葡萄球菌表现出选择性疗效（MIC分别<40和<47 μg/mL）。此外，对这些苯并噻唑并嘧啶衍生物与PDB编号为2XCT的蛋白质进行了分子对接，以发现它们的结合类型、均方根偏差（RMSD）、结合分数以及每种衍生物的相互作用口袋，包括一种药物参考。此外，已通过瑞士药物相似性评估工具（SwissADME）预测了它们的理化 - 药代动力学特征。数据表明，衍生物1显示出良好的药代动力学性质（分子量269.28）、亲脂性（Log Po/w = 1.45）以及拓扑极性表面积（TPSA）= 103.47，这预示着其具有高胃肠道（GI）吸收和良好的生物利用度 = 0.55，且未违反Lipinski规则。
