Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470, Eskisehir, Turkey.
Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto, 862-0973, Japan.
Mol Cell Biochem. 2023 May;478(5):1099-1108. doi: 10.1007/s11010-022-04580-4. Epub 2022 Oct 11.
Glioma is the fast-growing, aggressive, and prevalent brain cancer with a great level of morbidity and mortality. Current therapy is usually found insufficient for glioma treatment. In the course of our research attempting to identify effective anti-glioma agents, three benzothiazole derivatives (1-3) were examined on U251 glioma cells. Among these derivatives, compound 3 was found to have the strongest cytotoxic effect on glioma cells with an IC value of 9.84 ± 0.64 μM in reference to cisplatin (IC = 8.41 ± 1.27 μM). Further mechanism of anti-glioma effects of compound 3 was characterized by the determination of its apoptotic effects in glioma cells and DNA cleaving capacity. Compound 3 caused a significant apoptotic death of U251 cell line. Besides, this compound cleaved DNA with FeSO, HO and ascorbic acid system. Molecular docking results also showed that compound 3 possessed a significant binding potential to DNA via important π-π stacking interaction with DG-16. Some pharmacokinetic determinants of compound 3 complied with standard limits making it as an efficient bioavailable anti-glioma drug candidate for upcoming exploration.
神经胶质瘤是一种快速生长、侵袭性强且普遍存在的脑癌，发病率和死亡率都很高。目前的治疗方法通常被认为不足以治疗神经胶质瘤。在我们试图寻找有效抗神经胶质瘤药物的研究过程中，对三种苯并噻唑衍生物（1-3）进行了 U251 神经胶质瘤细胞的检测。在这些衍生物中，化合物 3 对神经胶质瘤细胞的细胞毒性最强，其 IC 值为 9.84±0.64 μM，而顺铂（IC=8.41±1.27 μM）。通过测定化合物 3 在神经胶质瘤细胞中的凋亡作用和 DNA 裂解能力，进一步研究了化合物 3 的抗神经胶质瘤作用机制。化合物 3 导致 U251 细胞系发生显著的凋亡性死亡。此外，该化合物在 FeSO、HO 和抗坏血酸体系中能裂解 DNA。分子对接结果还表明，化合物 3 通过与 DG-16 发生重要的π-π堆积相互作用，对 DNA 具有显著的结合潜力。化合物 3 的一些药代动力学决定因素符合标准限制，使其成为一种有效的、可供生物利用的抗神经胶质瘤药物候选物，值得进一步研究。
