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

Autor: Joshi PV; Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, India., Sayed AA; Department of Chemistry, Abeda Inamdar Senior College, Azam Campus, Pune 411001, India., RaviKumar A; Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, India., Puranik VG; Centre for Material Characterization, CSIR-National Chemical Laboratory, Pune 411 008, India., Zinjarde SS; Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, India.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2017 Aug 18; Vol. 136, pp. 246-258. Date of Electronic Publication: 2017 May 02.
DOI: 10.1016/j.ejmech.2017.05.002
Abstrakt: 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 1B and 5-HT 2B . 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.
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Databáze: MEDLINE
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