Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt.
Hormones Department, Medical Research Division, National Research Centre, Cairo, Egypt; Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Dokki, Cairo, Egypt.
Steroids. 2019 Dec;152:108485. doi: 10.1016/j.steroids.2019.108485. Epub 2019 Sep 3.
There is a pressing need to discover and develop novel drugs against cancer. With the new era of bioinformatics, which integrates different aspects, drug development has been tremendously improved. Recently, extensive research was directed towards the rational modification of steroid molecules against different disease especially cancer. Moreover, heterocyclic steroid derivatives have shown a lot of different biological activities such as antimicrobial, anti-inflammatory, and anti-cancer activities. Molecular docking methods can be used to explore how the steroid derivatives conformations can adopt within the binding sites of specific macromolecular targets involved in cancer progression. We conducted this study to investigate the accuracy of different molecular docking calculations using different steroidal molecular targets, and to define the most accurate one to study the mode of action of steroid derivatives as potential anti-cancer drugs. Our results revealed that the Dock6, PLANTS, AutoDock, GLIDE (SP and XP), and GOLD (ASP, Chemscore, and PLP) software were able to maintain the binding mode of the co-crystallized ligands inside their proteins by achieving RMSD values lower than two. Moreover, molecular docking study revealed that compound 4, and 5 are promising steroidal derivatives as anti-cancer drugs. Further on, the cytotoxic activity of the selected steroidal derivatives were tested against leukemia cell line using MTT assay. The results revealed that compound 4, and 5 were potential cytotoxic agents against THP-1 cells (ICs were 44.67 µM, and 46.77 µM, respectively), these results are in agreement with the molecular docking study.
迫切需要发现和开发针对癌症的新型药物。随着整合了不同方面的新时代生物信息学的出现，药物开发得到了极大的改善。最近，广泛的研究致力于合理修饰甾体分子以对抗不同的疾病，特别是癌症。此外，杂环甾体衍生物表现出许多不同的生物活性，如抗菌、抗炎和抗癌活性。分子对接方法可用于探索甾体衍生物构象如何在涉及癌症进展的特定大分子靶标的结合位点内适应。我们进行这项研究是为了研究使用不同的甾体分子靶标进行不同分子对接计算的准确性，并确定最准确的方法来研究甾体衍生物作为潜在抗癌药物的作用模式。我们的结果表明，Dock6、PLANTS、AutoDock、GLIDE（SP 和 XP）和 GOLD（ASP、Chemscore 和 PLP）软件能够通过实现低于 2 的 RMSD 值来保持共晶配体在其蛋白质内的结合模式。此外，分子对接研究表明，化合物 4 和 5 是有前途的甾体衍生物作为抗癌药物。此外，还使用 MTT 测定法测试了选定的甾体衍生物对白血病细胞系的细胞毒性。结果表明，化合物 4 和 5 是对 THP-1 细胞有潜在细胞毒性的试剂（IC 分别为 44.67µM 和 46.77µM），这些结果与分子对接研究一致。
