Journal
MOLECULAR PHARMACEUTICS
Volume -, Issue -, Pages -Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.2c00170
Keywords
photodynamic therapy; histone deacetylase inhibitors; pyropheophorbide a; pharmacophore fusion strategy
Ask authors/readers for more resources
The synthesis of dual-mode antitumor molecules combining photodynamic therapy and chemotherapy has shown promising results in inhibiting tumor growth and metastasis. Compound 4, with favorable phototoxicity and dark toxicity, demonstrated the best inhibitory effect on tumor growth and migration, making it a potential photosensitizer and HDACi.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available