1. Novel dual-mode antitumor chlorin-based derivatives as potent photosensitizers and histone deacetylase inhibitors for photodynamic therapy and chemotherapy.
- Author
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Zhang XJ, Liu MH, Luo YS, Han GY, Ma ZQ, Huang F, Wang Y, Miao ZY, Zhang WN, Sheng CQ, and Yao JZ
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Apoptosis drug effects, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Drug Screening Assays, Antitumor, Histone Deacetylase Inhibitors chemical synthesis, Histone Deacetylase Inhibitors chemistry, Humans, Molecular Structure, Photosensitizing Agents chemical synthesis, Photosensitizing Agents chemistry, Porphyrins chemical synthesis, Porphyrins chemistry, Reactive Oxygen Species metabolism, Structure-Activity Relationship, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylases metabolism, Photochemotherapy, Photosensitizing Agents pharmacology, Porphyrins pharmacology
- Abstract
The combination of photodynamic therapy (PDT) and chemotherapy is a prospective strategy to improve antitumor efficacy. Herein, a series of novel cytotoxic chlorin-based derivatives as dual photosensitizers (PSs) and histone deacetylase inhibitors (HDACIs) were synthesized and investigated for biological activity. Among them, compound 15e showed definite HDAC2 and 10 inhibitory activities by up-regulating expression of acetyl-H4 and highest phototoxicity and dark-toxicity, which was more phototoxic than Talaporfin as a PS while with stronger dark-toxicity compared to vorinostat (SAHA) as a HDACI. The biological assays demonstrated that 15e was liable to enter A549 cells and localized in mitochondria, lysosomes, golgi and endoplasmic reticulum (ER) etc. multiple organelles, resulting in higher cell apoptosis rate and ROS production compared to Talaporfin. Moreover, it could induce tumor cell autophagy as a dual PS and HDACI. All results suggested that compound 15e could be applied as a potential dual cytotoxic drug for PDT and chemotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
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