Center of Drug Discovery and Development, Research Institute for Health Sciences and Technologies SABITA, Istanbul Medipol University, 34810 Istanbul, Turkey.
Department of Molecular Medicine, and Biotechnology, Health Sciences Institute, Istanbul Medipol University, 34810 Istanbul, Turkey.
Molecules. 2022 Oct 27;27(21):7309. doi: 10.3390/molecules27217309.
To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound's best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds' molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone had the minimum IC value of 13.39 μM. For the MDA-MB-231 cell line, oxadiazole demonstrated the lowest IC value, with 22.73 μM. For PC-3, hydrazone showed the lowest C50 value of 9.38 μM. The three most promising compounds were determined as compounds , , and based on their minimum IC values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.
为了研究先前合成的新型腙和噁二唑衍生物是否具有有前景的抗癌作用，我们对 A-549、MDA-MB-231 和 PC-3 细胞系进行了对接研究和体外毒性检测。采用分子对接实验研究了这些化合物的抗增殖特性。评估了每个化合物的最佳对接构象、结合亲和力和受体-配体相互作用。还给出了化合物的分子量、logP 值、TPSA 值、通过血脑屏障的能力、GI 吸收质量和 CYP450 抑制能力。当在体外研究这些分子的活性时，对于 A-549 细胞系，腙 具有最低的 IC 值 13.39 μM。对于 MDA-MB-231 细胞系，噁二唑 显示出最低的 IC 值，为 22.73 μM。对于 PC-3，腙 显示出最低的 C50 值 9.38 μM。基于最低的 IC 值，确定了三种最有前途的化合物， 和 ，并对具有高迁移能力的 A-549 和 MDA-MB-231 细胞进行了划痕实验，结果表明这三种最有效的分子没有表现出明显的抗转移作用。
