Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, India.
Department of Chemistry, Abeda Inamdar Senior College, Azam Campus, Pune 411001, India.
Eur J Med Chem. 2017 Aug 18;136:246-258. doi: 10.1016/j.ejmech.2017.05.002. Epub 2017 May 2.
Antagonists of signaling receptors are often effective non-toxic therapeutic agents. Over the years, there have been evidences describing the role of serotonin or 5-hydroxytryptamine (5-HT) in development of cancer. Although there are reports on the antiproliferative effects of some serotonin receptor antagonists, there are very few investigations related to understanding their structure-activity relationships. In this study, we report the screening of a library of 4-phenyl quinoline derivatives for their antiproliferative activities. Preliminary docking studies indicated that these ligands had the ability to bind to two of the serotonin receptors, 5-HT and 5-HT. The results of the in silico experiments were validated by performing in vitro studies on MCF-7 breast cancer cell line. The ethylpiperazine derivatives showed maximum toxicity against this cancer cell line. The compounds inhibited Calcium ion efflux (induced by serotonin) and ERK activation. One of the most active 4-phenyl quinoline derivatives (H3a) also induced apoptosis, thereby, suggesting the use of this scaffold as a potential anticancer drug.
信号受体拮抗剂通常是有效且无毒的治疗药物。多年来，已有证据表明血清素或 5-羟色胺（5-HT）在癌症发展中的作用。虽然有一些关于某些 5-羟色胺受体拮抗剂的抗增殖作用的报道，但很少有研究涉及了解它们的结构-活性关系。在这项研究中，我们报告了对 4-苯基喹啉衍生物库进行的增殖活性筛选。初步对接研究表明，这些配体具有与两种血清素受体 5-HT 和 5-HT 结合的能力。通过在 MCF-7 乳腺癌细胞系上进行体外研究验证了计算机实验的结果。乙基哌嗪衍生物对这种癌细胞系显示出最大的毒性。这些化合物抑制钙离子外排（由血清素诱导）和 ERK 激活。最有效的 4-苯基喹啉衍生物之一（H3a）也诱导细胞凋亡，因此，建议使用这种支架作为潜在的抗癌药物。
