Glutathione S-Transferase π-Activatable O2-(Sulfonylethyl Derived) Diazeniumdiolates Potently Suppress Melanoma in Vitro and in Vivo
- Zhangjian Huang*
Zhangjian Huang*Z.H.: phone, +86-25-83271072; fax, +86-25-83271072; e-mail, [email protected]State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Zhangjian Huang
- ,
- Jianbing Wu
Jianbing WuState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Jianbing Wu
- ,
- Yu Zou
Yu ZouState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Yu Zou
- ,
- Haoliang Yuan
Haoliang YuanState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Haoliang Yuan
- ,
- Yinqiu Zhang
Yinqiu ZhangState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Yinqiu Zhang
- ,
- Yue Fei
Yue FeiState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Yue Fei
- ,
- Atul Bhardwaj
Atul BhardwajFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, CanadaMore by Atul Bhardwaj
- ,
- Jatinder Kaur
Jatinder KaurFaculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, CanadaMore by Jatinder Kaur
- ,
- Edward E. Knaus*
Edward E. Knaus*E.E.K.: phone, 1-780-492 5993; fax, +1-780-492 1217; e-mail, [email protected]Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, CanadaMore by Edward E. Knaus
- , and
- Yihua Zhang*
Yihua Zhang*Y.Z.: phone, +86-25-83271015; fax, +86-25-83271015; e-mail, [email protected]State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, ChinaMore by Yihua Zhang
Abstract
A group of glutathione S-transferase π (GSTπ) activatable O2-(sulfonylethyl derived) diazeniumdiolates 5–12 were designed and synthesized. These compounds could be activated by GSTπ to initiate the β-elimination reaction, liberating an active vinyl sulfone-based GSH derivative and a diazeniumdiolate anion which subsequently releases NO in situ. The most active compound 6 released relatively high levels of NO and inhibited proliferation of melanoma B16 cells, superior to a diazeniumdiolate-based anticancer agent JS-K (1). Importantly, 6 had 8-fold less inhibitory activity against normal epithelial JB6 Cl 30-7b cells. The inhibitory activity of 6 could be diminished by an NO scavenger or GSTπ inhibitor. Furthermore, 6 induced nitration of mitochondrial tyrosine in B16 cells and inoculated B16 tumors in mice, which might be responsible for oxidation of protein leading to tumor suppression. Finally, 6 significantly retarded the B16 cells growth in a mouse xenograft model. These findings suggest that 6 may have a potential to treat melanoma.
Cited By
This article is cited by 16 publications.
- Hui Ye, Jianbing Wu, Zhuangzhuang Liang, Yihua Zhang, Zhangjian Huang. Protein S-Nitrosation: Biochemistry, Identification, Molecular Mechanisms, and Therapeutic Applications. Journal of Medicinal Chemistry 2022, 65 (8) , 5902-5925. https://doi.org/10.1021/acs.jmedchem.1c02194
- Tao Sun, Tian Lv, Jianbing Wu, Mingchao Zhu, Yue Fei, Jie Zhu, Yihua Zhang, Zhangjian Huang. General Strategy for Integrated Bioorthogonal Prodrugs: Pt(II)-Triggered Depropargylation Enables Controllable Drug Activation In Vivo. Journal of Medicinal Chemistry 2020, 63 (22) , 13899-13912. https://doi.org/10.1021/acs.jmedchem.0c01435
- Wei Liu, Yu Zhang, Jiaming He, Yue Yu, Jiajun Yuan, Xiaoyi Ye, Ziwu Zhang, Liang Xue, Hua Cao. Transition-Metal-Free Three-Component Reaction: Additive Controlled Synthesis of Sulfonylated Imidazoles. The Journal of Organic Chemistry 2019, 84 (17) , 11348-11358. https://doi.org/10.1021/acs.joc.9b01818
- Pejman Ghaffari‐Bohlouli, Hafez Jafari, Oseweuba Valentine Okoro, Houman Alimoradi, Lei Nie, Guohua Jiang, Ashok Kakkar, Amin Shavandi. Gas Therapy: Generating, Delivery, and Biomedical Applications. Small Methods 2024, 1 https://doi.org/10.1002/smtd.202301349
- Shixin Liu, Guowei Li, Dong Ma. Controllable Nitric Oxide‐Delivering Platforms for Biomedical Applications. Advanced Therapeutics 2022, 5 (3) https://doi.org/10.1002/adtp.202100227
- Xiujie Zhou, Niuniu Zhang, Yuzhen Li, Zuyu Mo, Xianli Ma, Yanyan Chen, Yanli Xu. Metal-free synthesis of 3-sulfonyl-5-selanyl-4a,8a-dihydro-2H-chromen-6(5H)-ones via visible light driven intermolecular cascade cyclization of alkyne-tethered cyclohexadienones and selenosulfonates. Green Synthesis and Catalysis 2021, 2 (4) , 397-400. https://doi.org/10.1016/j.gresc.2021.07.004
- Jianbing Wu, Tao Sun, Chenxi Yang, Tian Lv, Yuyang Bi, Yuan Xu, Yong Ling, Jun Zhao, Rigang Cong, Yihua Zhang, Jianhua Wang, Hao Wen, Hulin Jiang, Fei Li, Zhangjian Huang. Tetrazine-mediated bioorthogonal removal of 3-isocyanopropyl groups enables the controlled release of nitric oxide in vivo. Biomaterials Science 2021, 9 (5) , 1816-1825. https://doi.org/10.1039/D0BM01841D
- Yueqi Yang, Zhangjian Huang, Li-Li Li. Advanced nitric oxide donors: chemical structure of NO drugs, NO nanomedicines and biomedical applications. Nanoscale 2021, 13 (2) , 444-459. https://doi.org/10.1039/D0NR07484E
- Jintong Du, Jing Guo, Dongwei Kang, Zhihong Li, Guan Wang, Jianbing Wu, Zhen Zhang, Hao Fang, Xuben Hou, Zhangjian Huang, Guobo Li, Xiaoyun Lu, Xinyong Liu, Liang Ouyang, Li Rao, Peng Zhan, Xiaojin Zhang, Yihua Zhang. New techniques and strategies in drug discovery. Chinese Chemical Letters 2020, 31 (7) , 1695-1708. https://doi.org/10.1016/j.cclet.2020.03.028
- Sabrina Dallavalle, Vladimir Dobričić, Loretta Lazzarato, Elena Gazzano, Miguel Machuqueiro, Ilza Pajeva, Ivanka Tsakovska, Nace Zidar, Roberta Fruttero. Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors. Drug Resistance Updates 2020, 50 , 100682. https://doi.org/10.1016/j.drup.2020.100682
- Prabaharan Thiruvengetam, Rajan Deepan Chakravarthy, Dillip Kumar Chand. A molybdenum based metallomicellar catalyst for controlled and chemoselective oxidation of activated alcohols in aqueous medium. Journal of Catalysis 2019, 376 , 123-133. https://doi.org/10.1016/j.jcat.2019.06.013
- Fumou Sun, Yang Wang, Xiaojun Luo, Zhaoxiong Ma, Yao Xu, Xinrong Zhang, Tian Lv, Yihua Zhang, Min Wang, Zhangjian Huang, Juan Zhang. Anti-CD24 Antibody–Nitric Oxide Conjugate Selectively and Potently Suppresses Hepatic Carcinoma. Cancer Research 2019, 79 (13) , 3395-3405. https://doi.org/10.1158/0008-5472.CAN-18-2839
- Hiroshi Tsugawa, Ryo Nakabayashi, Tetsuya Mori, Yutaka Yamada, Mikiko Takahashi, Amit Rai, Ryosuke Sugiyama, Hiroyuki Yamamoto, Taiki Nakaya, Mami Yamazaki, Rik Kooke, Johanna A. Bac-Molenaar, Nihal Oztolan-Erol, Joost J. B. Keurentjes, Masanori Arita, Kazuki Saito. A cheminformatics approach to characterize metabolomes in stable-isotope-labeled organisms. Nature Methods 2019, 16 (4) , 295-298. https://doi.org/10.1038/s41592-019-0358-2
- Lu Lu, Xuemin Rao, Rigang Cong, Chenxi Zhang, Zhimei Wang, Jinyi Xu, Genzoh Tanabe, Osamu Muraoka, Xiaoming Wu, Weijia Xie. Design, Synthesis and Biological Evaluation of Nitrate Derivatives of Sauropunol A and B as Potent Vasodilatory Agents. Molecules 2019, 24 (3) , 583. https://doi.org/10.3390/molecules24030583
- Keith S. Wong, Walid A. Houry. Recent Advances in Targeting Human Mitochondrial AAA+ Proteases to Develop Novel Cancer Therapeutics. 2019, 119-142. https://doi.org/10.1007/978-981-13-8367-0_8
- Na Li, Manyi Xu, Na Bao, Wei Shi, Qixing Li, Xiaowei Zhang, Jianbo Sun, Li Chen. Discovery of novel NO-releasing celastrol derivatives with Hsp90 inhibition and cytotoxic activities. European Journal of Medicinal Chemistry 2018, 160 , 1-8. https://doi.org/10.1016/j.ejmech.2018.10.013