Synthesis and biological evaluation of coumarin derivatives as anti-lung adenocarcinoma agents via induction of apoptosis and autophagy: in vitro and in vivo studies

Abstract

Lung cancer represents a significant public health challenge, with non-small cell lung cancer (NSCLC) being the predominant subtype, underscoring the urgent need for improved therapeutic strategies. The limited efficacy of conventional chemotherapy has catalyzed the exploration of alternative treatment modalities. Natural products play a pivotal role in drug discovery, with structural modifications being integral to pharmaceutical research. This study presents novel coumarin derivatives that exhibit potential as candidate molecules for the treatment of lung adenocarcinoma. Among the synthesized compounds, compound 4f demonstrated potent inhibitory effects on PC9 cells, with an IC₅₀ value of 4.08 μM. In vitro analyses demonstrated that 4f significantly inhibited the proliferation and migration of PC9 cells by downregulating the expression of mTOR, which subsequently induced autophagic cell death. In vivo studies indicated that 4f effectively targets mTOR, leading to the suppression of tumor growth while exhibiting a favorable safety profile. These findings support the advancement of new coumarin derivatives as promising therapeutic agents for lung adenocarcinoma.