Drug Discovery Lab, Department of Chemistry, Annamalai University, Annamalai Nagar, 608002, Tamil Nadu, India.
Department of Pharmacology, PSG College of Pharmacy, Coimbatore, 641004, Tamil Nadu, India.
Eur J Med Chem. 2019 Apr 15;168:1-10. doi: 10.1016/j.ejmech.2019.02.033. Epub 2019 Feb 15.
Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.
基于结构的分子对接方法揭示了 2-(苯氧甲基)-5-苯基-1,3,4-恶二唑衍生物的研究结果。这些化合物（7a-o）是通过常规方法合成并得到了很好的表征。化合物 7b 和 7m 通过单晶 XRD 分析得到了重新确认。对合成的化合物（7a-o）进行了 MCF-7 和 MDA-MB-453 的抗增殖活性评估。此外，对测试化合物进行了 Lipinski 五规则和药代动力学性质的预测。这些结果表明，化合物 7b 和 7d 表现出更强的细胞毒性，而 7d 表现出剂量依赖性活性和降低的细胞活力。此外，通过形态变化和 Western 印迹分析观察到诱导细胞凋亡的作用机制。这些发现可能为进一步的发展提供线索。
