Citation: Zhang Xingjie, Meng Zhi, Ma Zhiqiang, Liu Junhong, Han Guiyan, Ma Fujia, Jia Ningyang, Miao Zhenyuan, Zhang Wannian, Sheng Chunquan, Yao Jianzhong. Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer[J]. Chinese Chemical Letters, ;2019, 30(1): 247-249. doi: 10.1016/j.cclet.2018.04.029 shu

Design and synthesis of novel water-soluble amino acid derivatives of chlorin p6 ethers as photosensitizer

Zhang Xingjie ^a,1 ,
Meng Zhi ^a,1 ,
Ma Zhiqiang ^a,1 ,
Liu Junhong ^a ,
Han Guiyan ^a ,
Ma Fujia ^b ,
Jia Ningyang ³ ,
Miao Zhenyuan ^a ,
Zhang Wannian ^a,, ,
Sheng Chunquan ^a,, ,
Yao Jianzhong ^a,,

a.
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
b.
Department of Pharmacy, 455 th Hospital of Chinese People's Liberation Army, Shanghai 200052, China
c.
Department of Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 China

Corresponding author: Zhang Wannian, zhangwnk@hotmail.com Sheng Chunquan, shengcq@hotmail.com Yao Jianzhong, yaojz6601@sina.com

Received Date: 27 March 2018
Revised Date: 24 April 2018
Accepted Date: 24 April 2018
Available Online: 27 January 2018

Figures(2)

Eight new water-soluble amino acid conjugates 6a-h of chlorin p₆ ethers (5a-d) were synthesized and preliminarily investigated for their in vitro PDT antitumor activity and structure-activity relationship (SAR). The results showed that all compounds exhibited much higher phototoxicity against tumor cells than talaporfin. SAR analysis indicated that PDT antitumor effect enhanced with the increase of carbon chain length of alkoxyl ether bonds at 3¹-position, and L-aspartic acid was superior to L-glutamic acid. In particular, the IC₅₀ values of most phototoxic compound 6d were 0.20 mmol/L against A549 cell and 0.41 mmol/L against B16-F10 cell, which individually represented 31-and 24-fold increase of antitumor potency compared to talaporfin, suggesting that it was a promising candidate photosensitizer (PS) for PDT applications due to its strong absorption at long wavelength, high phototoxicity, low dark cytotoxicity and good water-solubility.
- Photodynamic therapy (PDT),
- Photosensitizer,
- Silkworm excrement,
- Chlorin p₆,
- Antitumor
1. [1]
  P. Agostinis, K. Berg, K.A. Cengel, et al., Cancer J. Clin. 61(2011) 250-281. doi: 10.3322/caac.v61:4
2. [2]
  R.W. Redmond, I.E. Kochevar, Photochem. Photobiol. 82(2006) 1178-1186. doi: 10.1562/2006-04-14-IR-874
3. [3]
  N. Drogat, C. Gady, R. Granet, V. Sol, Dyes Pigment. 98(2013) 609-614. doi: 10.1016/j.dyepig.2013.03.018
4. [4]
  K.T. Oliveira, P.B. Momo, F.F. Assis, et al., Curr. Org. Synth. 11(2014) 42-58. doi: 10.2174/15701794113106660085
5. [5]
  J.Z. Yao, W.N. Zhang, C.Q. Sheng, et al., Bioorg. Med. Chem. Lett. 18(2008) 293-297. doi: 10.1016/j.bmcl.2007.10.086
6. [6]
  J.L. Zhang, L. Deng, J.Z. Yao, et al., Bioorg. Med. Chem. 19(2011) 5520-5528.
7. [7]
  D. Kessel, Photochem. Photobiol. 49(2008) 447-452.
8. [8]
  R.R. Allison, G.H. Downie, R. Cuenca, et al., Photodiagn. Photodyn. 1(2004) 27-42. doi: 10.1016/S1572-1000(04)00007-9
9. [9]
  H. Abrahamse, M.R. Hamblin, J. Biochem, 473 (2016) 347-364.
10. [10]
  T. Hitoshi, I. Yasuaki, T. Takuya, et al., Bioorg. Med. Chem. 22(2014) 1421-1428.
11. [11]
  W.G. Roberts, F.Y. Shiau, J.S. Nelson, et al., J. Natl. Cancer Inst. 80(1988) 330-336. doi: 10.1093/jnci/80.5.330
12. [12]
  M. Kwitniewski, A. Juzeniene, L.W. Ma, et al., J. Photochem. Photobiol. B 94(2009) 214-222. doi: 10.1016/j.jphotobiol.2008.11.005
13. [13]
  Z. Meng, B. Yu, G.Y. Han, et al., J. Med. Chem. 59(2016) 4999-5010. doi: 10.1021/acs.jmedchem.6b00352
14. [14]
  Z. Meng, B. Shan, L. Zhang, et al., Chin. Chem. Lett. 27(2016) 623-626. doi: 10.1016/j.cclet.2016.03.019
15. [15]
  J.Z. Yao, W.H. Chen, X. He, et al., Acta Pharm. Sin. 35(2000) 63-66.
16. [16]
  J.Z. Yao, D.Y. Xu, W.H. Chen, et al., Chin. J. Pharm. 30(1999) 403-406.
17. [17]
  J.Z. Yao, J.F. Liu, W.N. Zhang, et al., Chin. J. Org. Chem. 21(2001) 458-462.
1. [1]
  Du Liu , Yuyan Li , Hankun Zhang , Benhua Wang , Chaoyi Yao , Minhuan Lan , Zhanhong Yang , Xiangzhi Song . Three-in-one erlotinib-modified NIR photosensitizer for fluorescence imaging and synergistic chemo-photodynamic therapy. Chinese Chemical Letters, 2025, 36(2): 109910-. doi: 10.1016/j.cclet.2024.109910
2. [2]
  Zhe Li , Ping-Zhao Liang , Li Xu , Fei-Yu Yang , Tian-Bing Ren , Lin Yuan , Xia Yin , Xiao-Bing Zhang . Three positive charge nonapoptotic-induced photosensitizer with excellent water solubility for tumor therapy. Chinese Chemical Letters, 2024, 35(8): 109190-. doi: 10.1016/j.cclet.2023.109190
3. [3]
  Huijie An , Chen Yang , Zhihui Jiang , Junjie Yuan , Zhongming Qiu , Longhao Chen , Xin Chen , Mutu Huang , Linlang Huang , Hongju Lin , Biao Cheng , Hongjiang Liu , Zhiqiang Yu . Luminescence-activated Pt(Ⅳ) prodrug for in situ triggerable cancer therapy. Chinese Chemical Letters, 2024, 35(7): 109134-. doi: 10.1016/j.cclet.2023.109134
4. [4]
  Li Fu , Ziye Su , Shuyang Wu , Yanfen Cheng , Chuan Hu , Jinming Zhang . Redox-responsive hyaluronic acid-celastrol prodrug micelles with glycyrrhetinic acid co-delivery for tumor combination therapy. Chinese Chemical Letters, 2025, 36(5): 110227-. doi: 10.1016/j.cclet.2024.110227
5. [5]
  Ziyong Li , Jinzhao Song , Xinyu Gao , Xiaoxie Ma , Keyu Liu , Ziwei Ma , Qilian Wang , Xinliang Zeng , Haining Zhang , Pei Zhang , Hui Guo , Jun Yin . Highly efficient green light-excited AIE photosensitizers derived from BF₂-curcuminoid for specific photodynamic eradication of Gram-negative bacteria. Chinese Chemical Letters, 2025, 36(5): 110073-. doi: 10.1016/j.cclet.2024.110073
6. [6]
  Qihang Wu , Hui Wen , Wenhai Lin , Tingting Sun , Zhigang Xie . Alkyl chain engineering of boron dipyrromethenes for efficient photodynamic antibacterial treatment. Chinese Chemical Letters, 2024, 35(12): 109692-. doi: 10.1016/j.cclet.2024.109692
7. [7]
  Yueying Wang , Jianming Xiong , Linwei Xin , Yuanyuan Li , He Huang , Wenjun Miao . Photosensitizer-synergized g-carbon nitride nanosheets with enhanced photocatalytic activity for eradicating drug-resistant bacteria and promoting wound healing. Chinese Chemical Letters, 2025, 36(4): 110003-. doi: 10.1016/j.cclet.2024.110003
8. [8]
  Cheng He , Renlan Huang , Lingling Wei , Qiuhui He , Jinbo Liu , Jiao Chen , Ge Gao , Cheng Yang , Wanhua Wu . Uncovering the mask of sensitizers to switch on the TTA-UC emission by supramolecular host-guest complexation. Chinese Chemical Letters, 2025, 36(4): 110103-. doi: 10.1016/j.cclet.2024.110103
9. [9]
  Yiling Li , Zekun Gao , Xiuxiu Yue , Minhuan Lan , Xiuli Zheng , Benhua Wang , Shuang Zhao , Xiangzhi Song . FRET-based two-photon benzo[a] phenothiazinium photosensitizer for fluorescence imaging-guided photodynamic therapy. Chinese Chemical Letters, 2024, 35(7): 109133-. doi: 10.1016/j.cclet.2023.109133
10. [10]
  Li Li , Jiale Wen , Xiaojun Zhang , Shuwen Fu , Zixuan Chen , Kai Huang , Luyue Fang , Tinghe Zhao , Peipei Zhang , Xingshu Li . A near-infrared naphthalocyanine photosensitizer with superior light absorption and renal clearance for type-Ⅰ photodynamic and photothermal combination therapy. Chinese Chemical Letters, 2025, 36(6): 110290-. doi: 10.1016/j.cclet.2024.110290
11. [11]
  Zekun Gao , Xiuli Zheng , Weimin Liu , Jie Sha , Shuaishuai Bian , Haohui Ren , Jiasheng Wu , Wenjun Zhang , Chun-Sing Lee , Pengfei Wang . GSH-activatable copper-elsinochrome off-on photosensitizer for combined specific NIR-Ⅱ two-photon photodynamic/chemodynamic therapy. Chinese Chemical Letters, 2025, 36(3): 109874-. doi: 10.1016/j.cclet.2024.109874
12. [12]
  Haoran Hou , Siwen Wei , Yutong Shao , Yingnan Wu , Gaobo Hong , Jing An , Jiarui Tian , Jianjun Du , Fengling Song , Xiaojun Peng . A 690-nm-excitable type Ⅰ & Ⅱ photosensitizer based on biotinylation of verteporfin for photodynamic therapy of deep-seated orthotopic breast tumors. Chinese Chemical Letters, 2025, 36(6): 110315-. doi: 10.1016/j.cclet.2024.110315
13. [13]
  Zhaomin Tang , Qian He , Jianren Zhou , Shuang Yan , Li Jiang , Yudong Wang , Chenxing Yao , Huangzhao Wei , Keda Yang , Jiajia Wang . Active-transporting of charge-reversal Cu(Ⅱ)-doped mesoporous silica nanoagents for antitumor chemo/chemodynamic therapy. Chinese Chemical Letters, 2024, 35(7): 109742-. doi: 10.1016/j.cclet.2024.109742
14. [14]
  Xin Lv , Hongxing Zhang , Kaibo Duan , Wenhui Dai , Zhihui Wen , Wei Guo , Junsheng Hao . Lighting the Way Against Cancer: Photodynamic Therapy. University Chemistry, 2024, 39(5): 70-79. doi: 10.3866/PKU.DXHX202309090
15. [15]
  Jing Zhang , Charles Wang , Yaoyao Zhang , Haining Xia , Yujuan Wang , Kun Ma , Junfeng Wang . Application of magnetotactic bacteria as engineering microrobots: Higher delivery efficiency of antitumor medicine. Chinese Chemical Letters, 2024, 35(10): 109420-. doi: 10.1016/j.cclet.2023.109420
16. [16]
  Di ZHANG , Tianxiang XIE , Xu HE , Wanyu WEI , Qi FAN , Jie QIAO , Gang JIN , Ningbo LI . Construction and antitumor activity of pH/GSH dual-responsive magnetic nanodrug. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 786-796. doi: 10.11862/CJIC.20240329
17. [17]
  Zhipeng Li , Qincong Feng , Jianliang Shen . A β-lactamase-activatable photosensitizer for the treatment of resistant bacterial infections. Chinese Chemical Letters, 2024, 35(11): 109602-. doi: 10.1016/j.cclet.2024.109602
18. [18]
  Panpan Wang , Hongbao Fang , Mengmeng Wang , Guandong Zhang , Na Xu , Yan Su , Hongke Liu , Zhi Su . A mitochondria targeting Ir(III) complex triggers ferroptosis and autophagy for cancer therapy: A case of aggregation enhanced PDT strategy for metal complexes. Chinese Chemical Letters, 2025, 36(1): 110099-. doi: 10.1016/j.cclet.2024.110099
19. [19]
  Jin Wang , Xiaoyan Pan , Junyu Zhang , Qingqing Zhang , Yanchen Li , Weiwei Guo , Jie Zhang . Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy. Chinese Chemical Letters, 2024, 35(8): 109187-. doi: 10.1016/j.cclet.2023.109187
20. [20]
  Fengqing Wang , Changxing Qi , Chunmei Chen , Qin Li , Qingyi Tong , Weiguang Sun , Zhengxi Hu , Minyan Wang , Hucheng Zhu , Lianghu Gu , Yonghui Zhang . Discovery and enantioselective total synthesis of antitumor agent asperfilasin A via a regio- and diastereoselective Nazarov cyclization. Chinese Chemical Letters, 2025, 36(6): 110252-. doi: 10.1016/j.cclet.2024.110252

Get Citation

PDF

XML

Metrics

PDF Downloads(3)
Abstract views(1125)
HTML views(75)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142