Coupling Chlorin-Based Photosensitizers and Histone Deacetylase Inhibitors for Photodynamic Chemotherapy.
Lei HouYunchang ZhangYing HuangZhen FangGuangze SangTianheng ChenZhiqiang MaFeng YangPublished in: Molecular pharmaceutics (2022)
Photodynamic therapy combined with chemotherapy is a promising strategy to improve the antitumor efficacy. On the basis of coupling the chlorin-based photosensitizer pyropheophorbide a (Pyro) and histone deacetylase inhibitors (HDACis) to fabricate dual-mode antitumor molecules, a series of dual-mode antitumor prodrug molecules were synthesized and assessed for antitumor activity in vitro and in vivo. The data demonstrated that compound 4 , with the most favorable phototoxicity and dark toxicity, could significantly inhibit the cell migration and upregulate the expression of acetyl-H3 protein, functioning as a photosensitizer and HDACi, respectively. Furthermore, compared with talaporfin, Pyro, and SAHA, compound 4 demonstrated the best inhibitory effect on tumor growth and metastasis in tumor-bearing mice; therefore, represented by compound 4 , this pharmacophore coupling strategy is much more promising and effective than the pharmacophore fusion strategy for fabricating photodynamic and chemotherapeutical dual-mode molecules.
Keyphrases
- photodynamic therapy
- histone deacetylase
- cell migration
- fluorescence imaging
- cancer therapy
- room temperature
- molecular docking
- molecular dynamics
- poor prognosis
- locally advanced
- electronic health record
- squamous cell carcinoma
- drug delivery
- big data
- type diabetes
- protein protein
- amino acid
- insulin resistance
- small molecule
- drug release
- electron transfer
- data analysis