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

• Published in: International journal of biological macromolecules 2023-03, Vol.230, p.123147-123147, Article 123147
• Main Authors: Zhang, Qizhi, Yu, Wenmei, Liu, Zhenhua, Li, Hui, Liu, Yihui, Liu, Xin, Han, Zhaoshun, He, Jun, Zeng, Yaofu, Guo, Yu, Liu, Yunmei
• Format: Article
• Language: English
• Subjects: A549 Cells; Antineoplastic Agents - chemistry; Cell Proliferation; ct-DNA; DNA - pharmacology; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Molecular docking; Molecular Structure; Photosensitizing Agents - chemistry; Porphyrin-chrysin derivatives; Porphyrins - chemistry; Porphyrins - pharmacology; Structure-Activity Relationship
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.123147

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.