Design, synthesis and antitumor activities of chlorin p6 ether derivatives as photosensitizer for photodynamic therapy
10.3969/j.issn.1006-0111.201907017
- VernacularTitle:二氢卟吩p6醚类光敏剂的合成及光动力抗癌活性研究
- Author:
Fujia MA
1
;
Zhi MENG
2
;
Xingjie ZHANG
2
;
Yuan WANG
3
;
Zhiqiang MA
2
;
Jianzhong YAO
4
,
5
Author Information
1. Department of Pharmacy, Naval Characteristic Medical Center of PLA, Shanghai 200052，China.
2. School of Pharmacy, Naval Medical University，Shanghai 200433, China.
3. School of Pharmacy, Ningxia Medical University, Yinchuan 750004,China.
4. School of Pharmacy, Naval Medical University，Shanghai 200433, China
5. School of Pharmacy, Ningxia Medical University, Yinchuan 750004,China.yaojz6601@sina.com
- Keywords:
photodynamic therapy (PDT);
photosensitizer;
chlorine p6;
ether derivatives;
antitumor
- From:
Journal of Pharmaceutical Practice
2020;38(1):52-56
- CountryChina
- Language:Chinese
-
Abstract:
Objective To designe, synthesize a series of chlorin p6 ether photosensitizers and preliminarily investigate their photodynamic antitumor activity based on previous research results that alkoxyl ether derivatives of 3-vinyl on chlorin f exhibited stronger photosensitive antitumor activity than parent compound. Methods Purpurin-18 (4) was obtained by oxidative degradation with air and alkali on pheophorbide a (5) which was prepared through acid hydrolysis of chlorophyll a from crude chlorophyll extracts in Chinese traditional herb named Silkworm excrement. Then, chlorin p6 trimethylester (2) were formed via basic hydrolysis of internal anhydride ring for lead compound 3 and following immediately methylation with CH2N2. The intermediate 2 reacted with 33% HBr, following nucleophilic substitution with various alkoxyl alcohol to get six title compounds (1). All title compounds were subjected to photodynamic antitumor activity screening for melanoma B16-F10 cell in vitro. Results All title compounds showed much higher phototoxicity against melanoma B16-F10 cells than talaporfin and verteporfin. Their structures were confirmed by 1H-NMR, 13C-NMR, ESI-MS and ESI-HRMS spectra. Conclusion Chlorin p6 ether compounds were promising candidate photosensitizers for PDT applications due to theirs high dark toxicity/phototoxicity ratio and excellent phototoxicity, which were worthy of further research and development.
