Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Molecular Pharmacology

Background:

• Quinoxaline derivatives are recognized for their diverse biological activities.
• Developing novel antiproliferative agents is crucial for cancer therapy.
• Understanding the mechanisms of action of new anticancer compounds is essential.

Purpose of the Study:

• To synthesize and evaluate novel quinoxaline derivatives for antiproliferative effects against human cancer cell lines.
• To identify potent compounds and elucidate their mechanism of action.
• To investigate the molecular interactions of the lead compound through molecular docking.

Main Methods:

• Synthesis of quinoxaline derivatives.
• In vitro antiproliferative assays against human cancer cell lines.
• Cell cycle analysis (G2/M phase arrest).
• Assessment of reactive oxygen species (ROS) production and mitochondrial membrane potential.
• Apoptosis assays.
• Western blot analysis for cell cycle-related proteins (e.g., p21).
• Molecular docking studies.

Main Results:

• Compound 12 demonstrated significant antiproliferative activity (IC50: 0.19-0.51 μM).
• Compound 12 inhibited tubulin polymerization, disrupted microtubule networks, and caused G2/M phase arrest.
• The compound induced reactive oxygen species (ROS) production and mitochondrial dysfunction.
• Compound 12 triggered apoptosis in a dose-dependent manner.
• Western blot analysis revealed upregulation of p21 and altered expression of cell cycle proteins.
• Molecular docking provided insights into the binding mode.

Conclusions:

• Compound 12 is a potent antiproliferative agent with a promising mechanism of action involving microtubule disruption and apoptosis induction.
• The quinoxaline scaffold is a valuable platform for developing novel anticancer drugs.
• Further investigation into compound 12 is warranted for potential cancer therapeutic applications.