4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity

Title4-Phenyl quinoline derivatives as potential serotonin receptor ligands with antiproliferative activity
Publication TypeJournal Article
Year of Publication2017
AuthorsJoshi, PV, Sayed, AA, RaviKumar, A, Puranik, VG, Zinjarde, SS
JournalEuropean Journal of Medicinal Chemistry
Volume136
Pagination246-258
Date PublishedAUG
Type of ArticleArticle
Abstract

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-HT1B and 5-HT2B. 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. (C) 2017 Elsevier Masson SAS. All rights reserved.

DOI10.1016/j.ejmech.2017.05.002
Type of Journal (Indian or Foreign)

Foreign

Impact Factor (IF)

3.902

Divison category: 
Center for Material Characterization (CMC)