Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok 10110, Thailand.
Bioorg Med Chem. 2019 Oct 1;27(19):115040. doi: 10.1016/j.bmc.2019.08.001. Epub 2019 Aug 3.
A library of bis-sulfonamides (9-26) were synthesized and tested for their aromatase inhibitory activities. Interestingly, all bis-sulfonamide derivatives inhibited the aromatase with IC range of 0.05-11.6 μM except for compound 23. The analogs 15 and 16 bearing hydrophobic chloro and bromo groups exhibited the potent aromatase inhibitory activity in sub-micromolar IC values (i.e., 50 and 60 nM, respectively) with high safety index. Molecular docking revealed that the chloro and bromo benzenesulfonamides (15 and 16) may play role in the hydrophobic interaction with Leu477 of the aromatase to mimic steroidal backbone of the natural substrate, androstenedione. QSAR study also revealed that the most potent activity of compounds was governed by van der Waals volume (GATS6v) and mass (Mor03m) descriptors. Finally, the two compounds (15 and 16) were highlighted as promising compounds to be further developed as novel aromatase inhibitors.
合成了一系列双磺酰胺（9-26），并测试了它们对芳香酶的抑制活性。有趣的是，除了化合物 23 之外，所有的双磺酰胺衍生物均具有芳香酶抑制活性，IC 范围为 0.05-11.6μM。带有疏水性氯和溴取代基的类似物 15 和 16 具有很强的芳香酶抑制活性，IC 值在亚微摩尔范围内（即分别为 50 和 60nM），安全性指数高。分子对接表明，氯苯和溴苯磺酰胺（15 和 16）可能通过与芳香酶的 Leu477 发生疏水相互作用来模拟天然底物雄烯二酮的甾体骨架。QSAR 研究还表明，化合物的最强活性受范德华体积（GATS6v）和质量（Mor03m）描述符控制。最后，这两种化合物（15 和 16）被认为是很有前途的化合物，可以进一步开发为新型芳香酶抑制剂。
