Synthesis and screening of novel anthraquinone-quinazoline multitarget hybrids as promising anticancer candidates

Area of Science:

• Medicinal Chemistry
• Oncology
• Molecular Biology

Background:

• Epidermal growth factor receptor (EGFR) overexpression is common in epithelial cancers, making it a key therapeutic target.
• Targeting EGFR is a crucial strategy in cancer therapy.

Purpose of the Study:

• To design and synthesize novel anthraquinone-quinazoline hybrids as potential anticancer agents.
• To evaluate the antiproliferative activity and EGFR downregulation effects of these hybrids.

Main Methods:

• Synthesis of a series of anthraquinone-quinazoline hybrids.
• Assessment of antiproliferative activity against cancer cell lines.
• Evaluation of EGFR and p-EGFR protein expression levels.
• Analysis of apoptosis induction, cytoskeleton rearrangement, DNA damage, and radiosensitivity.

Main Results:

• Most synthesized hybrids exhibited significant antiproliferative activity and reduced EGFR expression.
• Compound 7d demonstrated the most potent antiproliferation, significantly downregulating p-EGFR.
• Compound 7d induced apoptosis, disrupted the cytoskeleton, caused DNA damage, and enhanced radiosensitivity in A549 cells.

Conclusions:

• The novel anthraquinone-quinazoline hybrid 7d is a promising anticancer drug candidate.
• Compound 7d exhibits multitargeted biological activities, including antiproliferation, apoptosis induction, and radiosensitization.
• These findings support the development of 7d for cancer therapy.