In Vitro Cytotoxicity and Mechanistic Investigation of Quinazolin-4(1H)-One Linked Coumarin as a Potent Anticancer Agent

Abstract

Quinazolinone-coumarin conjugates synthesized through Late-Stage Functionalization approach are evaluated for their in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Among the synthesized compounds, eight displayed significant growth inhibitory activity across a spectrum of cancer types, with compound 23 demonstrating particularly notable cytotoxicity. Further investigation involved a five-dose assay of compound 23 against NCI-60 cancer cell lines, revealing its efficacy at different concentrations. Additionally, binding studies elucidated its interaction with Human Serum Albumin (HSA) and DNA. The results indicated a strong binding affinity of 23 with HSA, evidenced by a high binding constant (2.26 × 10⁵ M⁻¹). Moreover, its interaction with DNA occurred via intercalation, specifically between the base pairs of DNA strands, with a binding constant of 5.51 × 10⁴ M⁻¹. This suggests that compound 23 has the ability to bind to both DNA and transport proteins, making it a promising pharmacophore with potential therapeutic applications.