Advances in quinazolin-4-one scaffolds in breast cancer therapy: emerging designs, mechanistic perspectives and SAR trends (2015-2025).

Breast cancer is the most frequently occurring cancer worldwide and has become the second primary cause of cancer-associated fatalities among females. It mainly arises from the abnormal proliferation of epithelial cells in the breast tissue and differs in prognosis, biological behaviour and treatment. The study of quinazolinone derivatives has gained attention as promising anti-breast cancer agents by suppressing tumor cell growth and progression. The presence of a carbonyl group and a nitrogen atom in the quinazolinone scaffold contributes to hydrogen bonding with amino acid residues of target proteins indicating strong and specific target binding affinities of these compounds. This review highlights the structure-activity relationship (SAR) of different quinazolinone derivatives along with their binding interactions which indicate that the electronic and lipophilic characteristics of substituents on different positions of the quinazolinone core significantly affect their activity in breast cancer. The incorporation of electron-donating and electron-withdrawing groups on the phenyl ring at the third position of the quinazolinone ring can affect cellular permeability and interaction with biological targets. The introduction of different substituents to the quinazolinone moiety can improve selectivity and potency across breast cancer cell lines. Recent studies have suggested that quinazolinone derivatives act as promising therapeutic candidates for breast cancer therapy. Further optimization through SAR studies and detailed mechanistic investigations could facilitate the design of highly effective and selective anti-breast cancer agents with low toxicity.