Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka 72388, Saudi Arabia.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia.
Molecules. 2022 Apr 18;27(8):2606. doi: 10.3390/molecules27082606.
New furan-based derivatives have been, designed, synthesized, and evaluated for their cytotoxic and tubulin polymerization inhibitory activities. DNA flow cytometric study of pyridine carbohydrazide and -phenyl triazinone demonstrated G/M phase cell cycle disruptions. Accumulation of cells in the pre-G1 phase and positive annexin V/PI staining, which may be caused by degeneration or fragmentation of the genetic components, suggested that cell death occurs via an apoptotic cascade. Furthermore, compounds and had a strong pro-apoptotic impact through inducing the intrinsic mitochondrial mechanism of apoptosis. This mechanistic route was verified by an ELISA experiment that indicated a considerable rise in the levels of p53 and Bax and a drop in the level of Bcl-2 when compared with the control.
已经设计、合成了新型呋喃基衍生物，并对其细胞毒性和微管蛋白聚合抑制活性进行了评价。吡啶甲脒和 - 苯基三嗪酮的 DNA 流式细胞术研究表明，它们可以破坏 G/M 期细胞周期。细胞在 G1 期前积累，以及阳性的 Annexin V/PI 染色，可能是由于遗传成分的退化或碎裂所致，这表明细胞死亡是通过凋亡级联发生的。此外，化合物和通过诱导细胞色素 c 从线粒体释放到细胞质中，从而激活 caspase-9 和 caspase-3，从而引发凋亡蛋白酶级联反应，对细胞凋亡具有强烈的促进作用。与对照组相比，ELISA 实验表明，p53 和 Bax 的水平显著升高，Bcl-2 的水平降低，这验证了这种机制途径。
