Aggregation-Induced Luminescent 3-Phenylpyrano[4,3-b]quinolizine Derivatives as Photosensitizers with Anti-Cancer Properties

Photodynamic therapy (PDT) has garnered significant attention as an effective and safe method for cancer therapy, with ongoing efforts to develop new photosensitizers to enhance its efficacy. This study aimed to develop novel photosensitizers with aggregation-induced emission enhancement (AIEE) properties. A series of 3-phenyl pyrano[4,3-b]quinolizine compounds (<b>3</b>-<b>10</b>) were synthesized by reacting pyrones (<b>1a</b>-<b>e</b>) with 2-pyridylacetate (<b>2a</b>) or 2-pyridylacetonitrile (<b>2b</b>) and then evaluated for their potential as photosensitizers. Spectroscopic analyses revealed that all compounds emitted blue to green fluorescence in ethanol, with emission wavelengths ranging from 446 nm to 515 nm. Compounds <b>5</b> and <b>6</b>, lacking a substituent at position 5 of pyrano[4,3-b]quinolizine, exhibited AIEE behavior in aqueous solution. Furthermore, all compounds produced reactive oxygen species upon exposure to LED light. Notably, compounds <b>5</b> and <b>6</b> demonstrate high singlet oxygen (¹O₂) generation efficiency in water-rich solvents, where they tend to aggregate, contributing to their potential to destroy cancer cells. In vitro studies using human colon cancer cells (Colo205) demonstrated that <b>5</b> and <b>6</b> exhibited potent anti-tumor activity upon exposure to LED light. These findings suggest that compounds <b>5</b> and <b>6</b>, based on 3-phenyl pyrano[4,3-b]quinolizine, possessing AIEE properties, are potential new photosensitizers for PDT.