Design and synthesis of glycofullerene derivatives as novel photosensitizer for potential application in PDT to treat cancer

Xue Bai; Tian Yang; Xinle Shao; Bobo Jia; Huifang Hao; Faiz-Ur Rahman; Yongmin Zhang

doi:10.1016/j.ejmech.2024.117009

Design and synthesis of glycofullerene derivatives as novel photosensitizer for potential application in PDT to treat cancer

Eur J Med Chem. 2024 Nov 6:281:117009. doi: 10.1016/j.ejmech.2024.117009. Online ahead of print.

Authors

Xue Bai¹, Tian Yang¹, Xinle Shao¹, Bobo Jia¹, Huifang Hao¹, Faiz-Ur Rahman¹, Yongmin Zhang²

Affiliations

¹ Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, China.
² Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, College of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, China; Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France; Fuyang Institute & School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311422, Zhejiang, China; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education and Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou, Hainan, 571158, China. Electronic address: yongmin.zhang@upmc.fr.

PMID: 39536494
DOI: 10.1016/j.ejmech.2024.117009

Abstract

Cancer is one of the most aggressive diseases known to humanity, characterized by low survival rates and poor prognoses. Currently, platinum-based anticancer drugs and traditional photosensitizers used in photodynamic therapy (PDT) are the most widely employed treatment modalities. However, the platinum-based medications, particularly cisplatin, the most commonly used agent, have several drawbacks. These drawbacks may include systemic toxicity, which can manifest as nephrotoxicity, neurotoxicity, ototoxicity, or emesis during treatment. Such side effects can severely impair patients and significantly diminish the overall effectiveness of therapeutic interventions. In contrast, photodynamic therapy does not present these disadvantages. PDT offers numerous benefits, including reduced long-term morbidity, minimal systemic toxicity, low invasiveness, negligible drug resistance, and temporal and geographic selectivity, all of which enhance patients' quality of life. Consequently, the search for novel, effective, and practical photosensitizers is essential. Fullerenes possess unique physicochemical properties that make them highly suitable as photosensitizers. In this study, we developed a comprehensive and straightforward synthesis for two water-soluble sugar fullerene derivatives, designated as 12 and 13. Multiple analytical techniques, including ¹H NMR, ¹³C NMR, high-resolution mass spectrometry (HRMS), Fourier-transform infrared spectroscopy (FT-IR), and ultraviolet-visible (UV-Vis) spectroscopy, collectively confirmed the chemical structures of these derivatives and validated their successful synthesis. Upon exposure to white light irradiation at an intensity of 2.5J/cm², compound 13 demonstrated significant biological activity against three distinct tumor cell lines: HepG2, MKN45, and RPMI 4788, with IC₅₀ values of 5.65 μM, 2.43 μM, and 1.82 μM, respectively. This study establishes a foundation for the development of innovative clinical photosensitizers.

Keywords: Antitumor; Carbohydrate; Fullerene; Photodynamic therapy; Synthesis.