Synthesis, characterization, anti-proliferative, and apoptotic activity of a novel quinazoline-containing...

Area of Science:

• Medicinal Chemistry
• Oncology
• Molecular Biology

Background:

• Current VEGFR2 inhibitors for cancer treatment have limitations due to severe side effects.
• Designing novel inhibitors requires retaining key pharmacophoric features of existing drugs for optimal receptor binding.

Purpose of the Study:

• To synthesize and evaluate a novel quinazoline-containing 1,2,3-triazole (4-TCPA) as a VEGFR2 inhibitor for cancer therapy.
• To assess the anticancer efficacy and apoptotic induction of 4-TCPA in various cancer cell lines.

Main Methods:

• Synthesis of 4-TCPA based on structural analysis of effective VEGFR2 inhibitors.
• In vitro anticancer assays against A549, MCF7, K562 cancer cells and HFF2 normal cells.
• Mechanistic studies involving EGFR, mTOR, Akt, MAPK, PIK3CA, and VEGFR2 expression analysis using qRT-PCR and apoptosis assays (Annexin V/PI, caspase-3/7).

Main Results:

• 4-TCPA demonstrated significant inhibitory activity against A549 (IC50=35.70 μM), MCF7 (IC50=19.50 μM), and K562 (IC50=5.95 μM) cancer cells, with lower toxicity to HFF2 cells (IC50=135.2 μM).
• The compound induced both early and late apoptosis, confirmed by Annexin V/PI staining and caspase-3/7 activation.
• 4-TCPA effectively down-regulated key signaling pathway targets (EGFR, mTOR, Akt, MAPK, PIK3CA, VEGFR2) in a time-dependent manner.

Conclusions:

• 4-TCPA exhibits promising anticancer potential through targeted VEGFR2 inhibition and induction of apoptosis.
• The compound's ability to down-regulate multiple cancer-related signaling pathways suggests a broad therapeutic application.
• Further investigation into 4-TCPA is warranted to explore its efficacy as a novel anticancer agent.