Design, synthesis, antitumor activity and ct-DNA binding study of photosensitive drugs based on porphyrin framework.

Abstract

Photodynamic therapy is a promising novel tumor treatment method. In this study, novel porphyrin-chrysin photosensitizer derivatives were synthesized. Most of the compounds showed antitumor activity against human cervical cancer HeLa cells and human lung cancer A549 cells, among which compound 4c had the best photodynamic therapy effect on HeLa cells and A549 cells, with IC50 values of 6.26 μM and 23.37 μM, respectively. Free-base porphyrin-chrysin derivatives bind to DNA through surface self-stacking, and zinc metalloporphyrin-chrysin derivatives bind to ct-DNA through intercalation. Notably, the tightness of compound binding to ct-DNA was positively correlated with its antitumor activity. What's more, three-dimensional quantitative conformation studies have shown that increasing the positive charge of the porphyrin ring and introducing a strong electron-withdrawing group at the meso position of the porphyrin ring at the para-position of the benzene ring or reducing the space volume of the compound can enhance the antitumor activity.

• Authors: Qizhi Zhang, Wenmei Yu, Zhenhua Liu, Hui Li, Yihui Liu, Xin Liu, Zhaoshun Han, Jun He, Yaofu Zeng, Yu Guo, Yunmei Liu
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 230 Pg. 123147 (Mar 01 2023) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 36621729 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Porphyrins
• Photosensitizing Agents
• DNA
• Antineoplastic Agents

Topics

• Humans
• HeLa Cells
• Porphyrins (pharmacology, chemistry)
• Photosensitizing Agents (chemistry)
• A549 Cells
• DNA (pharmacology)
• Antineoplastic Agents (chemistry)
• Drug Screening Assays, Antitumor
• Structure-Activity Relationship
• Molecular Structure
• Cell Proliferation