小分子氢过硫化物供体的研究进展

doi:10.6023/cjoc202101008

摘要/Abstract

小分子氢过硫化物(RSSH)具有独特的化学性质, 近年来其生物学活性备受瞩目. 近五年间, 生理或病理条件下即可实现RSSH原位释放供体化合物取得了突破性的进展, 这类供体将成为研究RSSH生理功能、作用机制以及治疗潜能的有力工具. 按照激活模式将现有供体分子分为五类, 即酯酶激活型、ROS(活性氧物种)激活型、pH依赖型、光激活型以及硝基还原酶激活型, 并对各类供体进行综述. 现有供体在细胞水平表现出理想的抗氧化应激活性, 部分供体已经应用于心肌缺血再灌注模型的干预中, 并取得了积极效果. 此外, 还介绍了供体的释放机理及其概念验证过程, 并对供体分子的发展前景进行了展望.

关键词: 氢过硫化物, 供体, 氧化应激, 酯酶, 硫烷硫

The unique chemical structure endowed small-molecular hydropersulfides (RSSH) with unclear but fascinating biological activities, which have been attracted much attention. The donors that could release RSSH smoothlyin situ under physiological or pathological conditions will become powerful chemical tools for exploring the physiological functions, mechanism of action, and potential therapeutic benefit of RSSH. Over the past five years, a substantial breakthrough had been achieved in the design and development of RSSH donors, which is summarized in this perspective. According to the activation patterns, the existing donors are divided into five categories, namely esterase-activated donor, ROS (reactive oxygen species)-activated donor, pH-dependent donor, light-activated donor, and nitroreductase-activated donor. All kinds of donors played ideal roles in improving the oxidative stress at the cellular level, part of which also show a positive therapeutic effect in the context of myocardial ischemia-reperfusion injury. Besides, the related release mechanisms and the proof of concept of the donors are briefly introduced. In the next five years, waves of novel donors are emerging. On one hand, diverse donors, with stable and controllable release rate, clear release process, and identified release components, will be designed. On the other hand, the indispensable toolbox of donors will be fully assembled for more in-depth and comprehensive biological activity researches.

Key words: hydropersulfides, donor, oxidative stress, esterase, sulfane sulfur

引用此文

许亚文, 王健鲲, 甄乐, 王广基. 小分子氢过硫化物供体的研究进展[J]. 有机化学, 2021, 41(7): 2601-2609.

Yawen Xu, Jiankun Wang, Le Zhen, Guangji Wang. Research Progress of Small-Molecular Hydropersulfide Donors[J]. Chinese Journal of Organic Chemistry, 2021, 41(7): 2601-2609.

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图/表 14

图1. 氢过硫化物的化学特性

Figure 1. Chemical properties of RSSH

图2. 供体1与2的释放机制及捕获剂结构

Figure 2. Donors 1 and 2, their mechanisms of release, and the trapping agents

图3. 供体3及其释放机制

Figure 3. Donor 3 and its mechanism of release

图4. 供体4与5及其释放机制

Figure 4. Donors 4 and 5, and their mechanisms of release

图5. 供体6与探针7及其释放机制

Figure 5. Donor 6 and probe 7, and their mechanisms of release

图6. 供体8及其释放机制

Figure 6. Donor 8, and its mechanism of release

图7. 供体9、探针10~12及其释放机制

Figure 7. Donor 9, probes 10~12, and their mechanisms of release

图8. 供体13与14

Figure 8. Donor 13 and 14

图9. 供体15及其释放机制

Figure 9. Donor 15 and its mechanism of release

图10. 供体16及其释放机制

Figure 10. Donor 16 and its mechanism of release

图11. 供体17及其释放机制

Figure 11. Donor 17 and its mechanism of release

图12. 供体18及其释放机制

Figure 12. Donor 18 and its mechanism of release

图13. 供体19及其释放机制

Figure 13. Donor 19 and its mechanism of release

图14. 供体20及其释放机制

Figure 14. Donor 20 and its mechanism of release

参考文献 18

[19]	Dillon,K. M.; Carrazzone,R. J.; Wang, Y.; Powell,C. R.; Matson,J. B. ACS Macro Lett. 2020, 9,606. doi: 10.1021/acsmacrolett.0c00118
[20]	Powell,C. R.; Dillon,K. M.; Wang, Y.; Carrazzone,R. J.; Matson,J. B. Angew. Chem.,Int. Ed. 2018, 57,6324. doi: 10.1002/anie.v57.21
[21]	Kuivila,H. G. J. Am. Chem. Soc. 1954, 76,870. doi: 10.1021/ja01632a070
[22]	Monks,T. J.; Jones,D. C. Curr. Drug Metab. 2002, 3,425. doi: 10.2174/1389200023337388
[23]	Bora, P.; Chauhan, P.; Manna, S.; Chakrapani, H. Org. Lett. 2018, 20,7916. doi: 10.1021/acs.orglett.8b03471
[24]	Hankins,R. A.; Suarez,S. I.; Kalk,M. A.; Green,N. M.; Harty,M. N.; Lukesh,J. C. Angew. Chem.,Int. Ed. 2020, 59,22238. doi: 10.1002/anie.v59.49
[25]	(a) Fridovich, I. J. Biol. Chem. 1997, 272,18515. doi: 10.1074/jbc.272.30.18515
	(b) Bandyopadhyay, U.; Das, D.; Banerjee,R. K. Curr. Sci. 1999, 77,658.
[26]	Wang, Y.; Dillon,K. M.; Li, Z.; Winckler,E. W.; Matson,J. B. Angew. Chem.,Int. Ed. 2020, 59,16698.
[27]	Roger, T.; Raynaud, F.; Bouillaud, F.; Ransy, C.; Simonet, S.; Crespo, C.; Bourguignon, M.; Villeneuve, N.; Vilaine, J.; Artaud, I. ChemBioChem 2013, 14,2268. doi: 10.1002/cbic.v14.17
[28]	Artaud, I.; Galardon, E. ChemBioChem 2014, 15,2361. doi: 10.1002/cbic.201402312
[29]	Kang, J.; Xu, S.; Radford,M. N.; Zhang, W.; Kelly,S. S.; Day,J. J.; Xian, M. Angew. Chem.,Int. Ed. 2018, 57,5893. doi: 10.1002/anie.201802845
[30]	Khodade,V. S.; Toscano,J. P. J. Am. Chem. Soc. 2018, 140,17333. doi: 10.1021/jacs.8b08469
[31]	Khodade,V. S.; Pharoah,B. M.; Paolocci, N.; Toscano,J. P. J. Am. Chem. Soc. 2020, 142,4309. doi: 10.1021/jacs.9b12180
[32]	Chaudhuri, A.; Venkatesh, Y.; Das, J.; Gangopadhyay, M.; Maiti,T. K.; Singh,N. D.P. J. Org. Chem. 2019, 84,11441. doi: 10.1021/acs.joc.9b01224
[33]	Fan, Y.; Pedersen, O. Nat. Rev. Microbiol. 2021, 19,55. doi: 10.1038/s41579-020-0433-9
[1]	The representative reviews of hydrogen persulfides in recent years see: (a) Saund,S. S.; Sosa, V.; Henriquez, S.; Nguyen,Q. N. N.; Bianco,C. L.; Soeda, S.; Millikin, R.; White, C.; Le, H.; Ono, K.; Tantillo,D. J.; Kumagai, Y.; Akaike, T.; Lin, J.; Fukuto,J. M.. Arch. Biochem. Biophys. 2015, 588,15. doi: 10.1016/j.abb.2015.10.016
	(b) Kasamatsu, S.; Nishimura, A.; Morita, M.; Matsunaga, T.; Hamid,H. A.; Akaike, T. Molecules 2016, 21,1721. doi: 10.3390/molecules21121721
	(c) Fukuto,J. M.; Ignarro,L. J.; Nagy, P.; Wink,D. A.; Kevil,C. G.; Feelisch, M.; Cortese-Krott,M. M.; Bianco,C. L.; Kumagai, Y.; Hobbs,A. J.; Lin, J.; Ida, T.; Akaike, T. FEBS Lett. 2018, 592,2140. doi: 10.1002/feb2.2018.592.issue-12
	(d) Filipovic,M. R.; Zivanovic, J.; Alvarez, B.; Banerjee, R. Chem. Rev. 2018, 118,377.
	(e) Lau, N.; Pluth,M. D. Curr. Opin. Chem. Biol. 2019, 49,1. doi: 10.1016/j.cbpa.2018.08.012
	(f) Sawa, T.; Motohashi, H.; Ihara, H.; Akaike, T. Biomolecules 2020, 10,1245. doi: 10.3390/biom10091245
[2]	(a) Iciek, M.; Bilska-Wilkosz, A.; Gorny, M. Acta Biochim. Pol. 2019, 66,533.
	(b) Shinkai, Y.; Kumagai, Y. Toxicol. Sci. 2019, 170,3. doi: 10.1093/toxsci/kfz091
[3]	(a) Ono, K.; Akaike, T.; Sawa, T.; Kumagai, Y.; Wink,D. A.; Tantillo,D. J.; Hobbs,A. J.; Nagy, P.; Xian, M.; Lin, J.; Fukuto,J. M. Free Radical Biol. Med. 2014, 77,82. doi: 10.1016/j.freeradbiomed.2014.09.007
	(b) Park,C. -M.; Weerasinghe, L.; Day,J. J.; Fukuto,J. M.; Xian, M. Mol. Biosyst. 2015, 11,1775. doi: 10.1039/C5MB00216H
	(c) Cuevasanta, E.; Moller,M. N.; Alvarez, B. Arch. Biochem. Biophys. 2017, 617,9. doi: 10.1016/j.abb.2016.09.018
[4]	(a) Everett,S. A.; Folkes,L. K.; Wardman, P.; Asmus,K. D. Free Radical Res. 1994, 20,387. doi: 10.3109/10715769409145638
	(b) Cuevasanta, E.; Lange, M.; Bonanata, J.; Laura Coitino, E.; Ferrer-Sueta, G.; Filipovic,M. R.; Alvarez, B. J. Biol. Chem. 2015, 290,26866. doi: 10.1074/jbc.M115.672816
	(c) Benchoam, D.; Semelak,J. A.; Cuevasanta, E.; Mastrogiovanni, M.; Grassano,J. S.; Ferrer-Sueta, G.; Zeida, A.; Trujillo, M.; Moller,M. N.; Estrin,D. A.; Alvarez, B. J. Biol. Chem. 2020, 295,15466. doi: 10.1074/jbc.RA120.014728
[5]	(a) Everett,S. A.; Wardman, P. Method Enzymol. 1995, 251,55.
	(b) Jin, F.; Asatryan, R.; Bozzelli,J. W. Int. J. Quantum Chem. 2012, 112,1945. doi: 10.1002/qua.v112.8
	(c) Alvarez, L.; Bianco,C. L.; Toscano,J. P.; Lin, J.; Akaike, T.; Fukuto,J. M. Antioxid. Redox Signaling 2017, 27,622. doi: 10.1089/ars.2017.7081
[6]	Ida, T.; Sawa, T.; Ihara, H.; Tsuchiya, Y.; Watanabe, Y.; Kumagai, Y.; Suematsu, M.; Motohashi, H.; Fujii, S.; Matsunaga, T.; Yamamoto, M.; Ono, K.; Devarie-Baez,N. O.; Xian, M.; Fukuto,J. M.; Akaike, T. Proc. Natl. Acad. Sci. U. S. A. 2014, 111,7606. doi: 10.1073/pnas.1321232111
[7]	(a) Chen,X. L.; Jhee,K. H.; Kruger,W. D. J. Biol. Chem. 2004, 279,52082. doi: 10.1074/jbc.C400481200
	(b) Singh, S.; Padovani, D.; Leslie,R. A.; Chiku, T.; Banerjee, R. J. Biol. Chem. 2009, 284,22457. doi: 10.1074/jbc.M109.010868
	(c) Mishanina,A. V.; Libiad, M.; Banerjee, R. Nat. Chem. Biol. 2015, 11,457. doi: 10.1038/nchembio.1834
[8]	Akaike, T.; Ida, T.; Wei,F. -Y.; Nishida, M.; Kumagai, Y.; Alam,M. M.; Ihara, H.; Sawa, T.; Matsunaga, T.; Kasamatsu, S.; Nishimura, A.; Morita, M.; Tomizawa, K.; Nishimura, A.; Watanabe, S.; Inaba, K.; Shima, H.; Tanuma, N.; Jung, M.; Fujii, S.; Watanabe, Y.; Ohmuraya, M.; Nagy, P.; Feelisch, M.; Fukuto,J. M.; Motohashi, H. Nat. Commun. 2017, 8,1177. doi: 10.1038/s41467-017-01311-y
[9]	(a) Toohey,J. I. Anal. Biochem. 2011, 413,1. doi: 10.1016/j.ab.2011.01.044
	(b) Greiner, R.; Palinkas, Z.; Baesell, K.; Becher, D.; Antelmann, H.; Nagy, P.; Dick,T. P. Antioxid. Redox Signaling 2013, 19,1749. doi: 10.1089/ars.2012.5041
	(c) Kimura, H. Free Radical Biol. Med. 2016, 96,S4.
	(d) Yadav,P. K.; Martinov, M.; Vitvitsky, V.; Seravalli, J.; Wedmann, R.; Filipovic,M. R.; Banerjee, R. J. Am. Chem. Soc. 2016, 138,289. doi: 10.1021/jacs.5b10494
[10]	(a) Hildebrandt,T. M.; Grieshaber,M. K. FEBS J. 2008, 275,3352;. doi: 10.1111/j.1742-4658.2008.06482.x
	(b) Libiad, M.; Yadav,P. K.; Vitvitsky, V.; Martinov, M.; Banerjee, R. J. Biol. Chem. 2014, 289,30901. doi: 10.1074/jbc.M114.602664
	(c) Landry,A. P.; Moon, S.; Kim, H.; Yadav,P. K.; Guha, A.; Cho,U. -S.; Banerjee, R. Cell Chem. Biol. 2019, 26,1515. doi: 10.1016/j.chembiol.2019.09.010
[11]	(a) Ihara, H.; Kasamatsu, S.; Kitamura, A.; Nishimura, A.; Tsutsuki, H.; Ida, T.; Ishizaki, K.; Toyama, T.; Yoshida, E.; Hamid,H. A.; Jung, M.; Matsunaga, T.; Fuji, S.; Sawa, T.; Nishida, M.; Kumagai, Y.; Akaike, T. Chem. Res. Toxicol. 2017, 30,1673. doi: 10.1021/acs.chemrestox.7b00120
	(b) Nishida, M.; Nishimura, A.; Matsunaga, T.; Motohashi, H.; Kasamatsu, S.; Akaike, T. Free Radical Biol. Med. 2017, 109,132. doi: 10.1016/j.freeradbiomed.2017.01.024
	(c) Khan, S.; Fujii, S.; Matsunaga, T.; Nishimura, A.; Ono, K.; Ida, T.; Ahmed,K. A.; Okamoto, T.; Tsutsuki, H.; Sawa, T.; Akaike, T. Cell Chem. Biol. 2018, 25,1403. doi: 10.1016/j.chembiol.2018.08.007
[34]	Dillon,K. M.; Morrison,H. A.; Powell,C. R.; Carrazzone,R. J.; Ringel-Scaia,V. M.; Winckler,E. W.; Council-Troche,R. M.; Allen,I. C.; Matson,J. B. Angew. Chem.,Int. Ed. 2021, 60,6061.
[11]	(d) Kasamatsu, S. Antioxid. Redox Signaling 2020, 33,1320. doi: 10.1089/ars.2020.8130
	(e) Kanda, H.; Kumagai, Y. Yakugaku Zasshi 2020, 140,1119. doi: 10.1248/yakushi.20-00096
[12]	(a) Sawa, T.; Zaki,M. H.; Okamoto, T.; Akuta, T.; Tokutomi, Y.; Kim-Mitsuyama, S.; Ihara, H.; Kobayashi, A.; Yamamoto, M.; Fujii, S.; Arimoto, H.; Akaike, T. Nat. Chem. Biol. 2007, 3,727. doi: 10.1038/nchembio.2007.33
	(b) Fujii, S.; Sawa, T.; Ihara, H.; Tong,K. I.; Ida, T.; Okamoto, T.; Ahtesham,A. K.; Ishima, Y.; Motohashi, H.; Yamamoto, M.; Akaike, T. J. Biol. Chem. 2010, 285,23970. doi: 10.1074/jbc.M110.145441
	(c) Fujii, S.; Sawa, T.; Nishida, M.; Ihara, H.; Ida, T.; Motohashi, H.; Akaike, T. Arch. Biochem. Biophys. 2016, 595,140. doi: 10.1016/j.abb.2015.11.008
[13]	(a) Abiko, Y.; Yoshida, E.; Ishii, I.; Fukuto,J. M.; Akaike, T.; Kumagai, Y. Chem. Res. Toxicol. 2015, 28,1301. doi: 10.1021/acs.chemrestox.5b00101
	(b) Millikin, R.; Bianco,C. L.; White, C.; Saund,S. S.; Henriquez, S.; Sosa, V.; Akaike, T.; Kumagai, Y.; Soeda, S.; Toscano,J. P.; Lin, J.; Fukuto,J. M. Free Radical Biol. Med. 2016, 97,136. doi: 10.1016/j.freeradbiomed.2016.05.013
	(c) Zivanovic, J.; Kouroussis, E.; Schott-Roux, S.; Filipovic,M. R. Free Radical Biol. Med. 2017, 112,187.
	(d) Ju, Y.; Fu, M.; Stokes, E.; Wu, L.; Yang, G. Molecules 2017, 22,1334. doi: 10.3390/molecules22081334
	(e) Aroca, A.; Gotor, C.; Romero,L. C. Front. Plant Sci. 2018, 9,1369. doi: 10.3389/fpls.2018.01369
	(f) Kimura, H. Brit. J. Pharmacol. 2020, 177,720. doi: 10.1111/bph.v177.4
	(g) Pedre, B.; Dick,T. P. Biol. Chem. 2021, 402,223. doi: 10.1515/hsz-2020-0249
[14]	(a) Bailey,T. S.; Zalcharov,L. N.; Pluth,M. D. J. Am. Chem. Soc. 2014, 136,10573. doi: 10.1021/ja505371z
	(b) Bailey,T. S.; Pluth,M. D. Free Radical Biol. Med. 2015, 89,662. doi: 10.1016/j.freeradbiomed.2015.08.017
[15]	(a) Liang, D.; Wu, H.; Wong,M. W.; Huang, D. Org. Lett. 2015, 17,4196. doi: 10.1021/acs.orglett.5b01962
	(b) Cai,Y. -R.; Hu,C. -H. J. Phys. Chem. B 2017, 121,6359. doi: 10.1021/acs.jpcb.7b03683
	(c) Cerda,M. M.; Hammers,M. D.; Earp,M. S.; Zakharov,L. N.; Pluth,M. D. Org. Lett. 2017, 19,2314. doi: 10.1021/acs.orglett.7b00858
	(d) Nagai, S.; Yoshida, M.; Takigawa, Y.; Torii, S.; Koshiishi, I. Food Chem. 2020,128511.
[16]	Zheng, Y.; Yu, B.; Li, Z.; Yuan, Z.; Organ,C. L.; Trivedi,R. K.; Wang, S.; Lefer,D. J.; Wang, B. Angew. Chem.,Int. Ed. 2017, 56,11749. doi: 10.1002/anie.201704117
[17]	Yuan, Z.; Zheng, Y.; Yu, B.; Wang, S.; Yang, X.; Wang, B. Org. Lett. 2018, 20,6364. doi: 10.1021/acs.orglett.8b02611
[18]	Jarosz,A. P.; Wei, W.; Gauld,J. W.; Auld, J.; Ozcan, F.; Aslan, M.; Mutus, B. Free Radical Biol. Med. 2015, 89,512. doi: 10.1016/j.freeradbiomed.2015.09.007