Alkahtani Hamad M, Alanazi Mohammed M, Aleanizy Fadilah Sfouq, Alqahtani Fulwah Yahya, Alhoshani Ali, Alanazi Fawaz E, Almehizia Abdulrahman A, Abdalla Ashraf N, Alanazi Mashael G, El-Azab Adel S, Abdel-Aziz Alaa A-M
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Saudi Pharm J. 2019 Jul;27(5):682-693. doi: 10.1016/j.jsps.2019.04.003. Epub 2019 Apr 3.
A new series of 5,5-diphenylhydantoin derivatives containing benzylidene or isatin (-) was synthesized. Their anticancer activity against HeLa, a cervical cancer cell line, A549, a lung cancer cell line, and MDA-MB-231, a breast cancer cell line, was evaluated. Compounds , , and exhibited potent anticancer activity with average IC values against the tested cell lines of 109, 59, 81 and 113 μM, respectively. Compound showed potent EGFR and VEGFR2 inhibitory activity with IC values of 6.17 and 0.09 μM, respectively. In addition, compound induced caspase-dependent apoptosis and reactive oxygen species (ROS) production at 5 and 10 μM. Moreover, a molecular docking simulation was performed for compound and sunitinib to predict the protein-ligand interactions with the active site of VEGFR2.
合成了一系列新的含有亚苄基或异吲哚酮（-）的5,5-二苯基乙内酰脲衍生物。评估了它们对宫颈癌细胞系HeLa、肺癌细胞系A549和乳腺癌细胞系MDA-MB-231的抗癌活性。化合物 、 、 和 表现出强大的抗癌活性，对测试细胞系的平均IC值分别为109、59、81和113 μM。化合物 表现出强大的EGFR和VEGFR2抑制活性，IC值分别为6.17和0.09 μM。此外，化合物 在5和10 μM时诱导了半胱天冬酶依赖性凋亡和活性氧（ROS）生成。此外，对化合物 和舒尼替尼进行了分子对接模拟，以预测与VEGFR2活性位点的蛋白质-配体相互作用。
