Hassanin Hany M, Serya Rabah A T, Abd Elmoneam Wafaa R, Mostafa Mai A
Department of Chemistry, Faculty of Education, Ain Shams University Roxy Cairo 11711, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
R Soc Open Sci. 2018 Jun 20;5(6):172407. doi: 10.1098/rsos.172407. eCollection 2018 Jun.
A series of novel pyranoquinolinone-based Schiff's bases were designed and synthesized. They were evaluated for topoisomerase IIβ (TOP2B) inhibitory activity, and cytotoxicity against breast cancer cell line (MCF-7) for the development of novel anticancer agents. A molecular docking study was employed to investigate their binding and functional properties as TOP2B inhibitors, using the Discovery Studio 2.5 software, where they showed very interesting ability to intercalate the DNA-topoisomerase complex. Compounds , and showed high docking score values (82.36% -29.98 kcal mol for compound , 78.18% -26.98 kcal mol for compound and 78.65, -28.11 kcal mol for compound ) and revealed the highest enzyme inhibition activity. The best hit compounds exhibited highly potent TOP2B inhibitors with submicromolar IC50 at 5 µM compared to the reference doxorubicin.
设计并合成了一系列基于吡喃喹啉酮的新型席夫碱。对它们进行了拓扑异构酶IIβ（TOP2B）抑制活性评估，以及针对乳腺癌细胞系（MCF-7）的细胞毒性测试，以开发新型抗癌药物。利用Discovery Studio 2.5软件进行分子对接研究，以研究它们作为TOP2B抑制剂的结合和功能特性，结果显示它们具有非常有趣的嵌入DNA-拓扑异构酶复合物的能力。化合物、和显示出高对接得分值（化合物为82.36% -29.98 kcal mol，化合物为78.18% -26.98 kcal mol，化合物为78.65, -28.11 kcal mol），并显示出最高的酶抑制活性。与参考药物阿霉素相比，最佳命中化合物表现出高效的TOP2B抑制剂，在5 µM时IC50为亚微摩尔。
