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

Area of Science:

• Medicinal Chemistry
• Pharmacology
• Oncology

Background:

• Serotonin (5-hydroxytryptamine) plays a role in cancer development.
• Serotonin receptor antagonists show antiproliferative effects, but structure-activity relationships are underexplored.

Purpose of the Study:

• Screen a library of 4-phenyl quinoline derivatives for antiproliferative activity.
• Investigate the potential of these compounds as anticancer agents targeting serotonin receptors.

Main Methods:

• In silico docking studies to predict binding to serotonin receptors (5-HT_1B and 5-HT_2B).
• In vitro antiproliferative assays using MCF-7 breast cancer cell line.
• Assessment of calcium ion efflux and ERK activation inhibition.
• Apoptosis induction analysis.

Main Results:

• 4-phenyl quinoline derivatives were screened for antiproliferative effects.
• Docking studies suggested binding to 5-HT_1B and 5-HT_2B receptors.
• Ethylpiperazine derivatives exhibited maximum toxicity against MCF-7 cells.
• Active compounds inhibited serotonin-induced calcium ion efflux and ERK activation.
• Compound H3a induced apoptosis.

Conclusions:

• 4-phenyl quinoline derivatives show promise as anticancer agents.
• The ethylpiperazine subclass demonstrated significant efficacy against breast cancer cells.
• Inhibition of serotonin receptors and downstream signaling pathways contributes to the observed anticancer effects.