Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, 110 025, New Delhi, India.
Centre for Interdisciplinary Research in Basic Science, Jamia Nagar, 110 025, New Delhi, India.
Eur J Med Chem. 2018 Jul 15;155:13-23. doi: 10.1016/j.ejmech.2018.05.034. Epub 2018 May 22.
In the quest for novel effective carbonic anhydrase inhibitors, some sulfonamide derivatives of pyridyl-indole based chalcone were synthesized and screened in vitro for inhibitory activity against human carbonic anhydrase IX isoform. Among all the synthesized compounds (SC2 -SC11), only three compounds SC3, SC7 and SC10 were found to have better binding affinity as shown by molecular docking and fluorescence binding studies. Further, the enzyme inhibition assay and in vitro anti-tumor evaluation against MCF-7 and HepG-2 cell lines revealed that the compounds SC3, SC7 and SC10 inhibited the CA IX selectively, possessed predominant anti-proliferative potential and significantly induced apoptosis in cancerous cells.
在寻找新型有效碳酸酐酶抑制剂的过程中,我们合成了一些基于吡啶-吲哚的查尔酮的磺胺衍生物,并在体外筛选其对人碳酸酐酶 IX 同工型的抑制活性。在所合成的化合物(SC2-SC11)中,只有三种化合物 SC3、SC7 和 SC10 被发现具有更好的结合亲和力,这一点通过分子对接和荧光结合研究得到了证实。此外,酶抑制测定和对 MCF-7 和 HepG-2 细胞系的体外抗肿瘤评估表明,化合物 SC3、SC7 和 SC10 选择性抑制 CAIX,具有显著的抗增殖潜力,并能显著诱导癌细胞凋亡。