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Review Article

寻找被忽视的热带病新疗法的药物发现努力——半胱氨酸蛋白酶抑制剂

卷 31, 期 16, 2024

发表于: 15 November, 2023

页: [2170 - 2194] 页: 25

弟呕挨: 10.2174/0109298673249097231017051733

摘要

背景:被忽视的热带病是人类的严重负担，影响到全球越来越多的人。许多这些疾病是由原生动物寄生虫引起的，其中半胱氨酸蛋白酶在寄生虫的发病机制中起着关键作用。 目的:在这篇综述文章中，我们总结了2017 - 2022年研究界的药物发现工作，特别关注小分子半胱氨酸蛋白酶抑制剂在选择性谱或药物样性质以及体内研究方面的优化。用这种方法评估的半胱氨酸蛋白酶包括来自曼氏血吸虫的组织蛋白酶B1、木瓜蛋白酶、cruzain、falcipain和rhodesain。 方法:以2017 - 2022年“半胱氨酸蛋白酶”和“被忽视的热带病”为关键词进行详尽的文献检索。总的来说，大约有3000篇科学论文被检索到，这些论文使用特定的关键词进行过滤，使重点放在药物发现工作上。 结果与结论:发现了治疗被忽视的热带病的有效和选择性半胱氨酸蛋白酶抑制剂，并进行了药代动力学和体内疗效研究。据作者所知，这些抑制剂都没有达到积极的临床开发阶段。抑制剂的效力或药代动力学性质或安全性或其组合阻止了化合物的进一步开发。需要更多的努力，特别强调优化药代动力学和安全特性，可能通过学术和工业研究小组的合作，具有互补的专业知识。此外，应开发与催化半胱氨酸反应的新型弹头，以推进研究领域，以便对社会产生有意义的影响。

关键词: 半胱氨酸蛋白酶，SmCB1，木瓜蛋白酶，cruzain, falcipain, rhodesain。

« Previous Next »
[1]
2023. Neglected tropical diseases. Available from: https://www.who.int/news-room/questions-and-answers/item/neglected-tropical-diseases (Accessed on: 2023- 02-01).
[2]
Mora, C.; McKenzie, T.; Gaw, I.M.; Dean, J.M.; von Hammerstein, H.; Knudson, T.A.; Setter, R.O.; Smith, C.Z.; Webster, K.M.; Patz, J.A.; Franklin, E.C. Over half of known human pathogenic diseases can be aggravated by climate change. Nat. Clim. Chang., 2022, 12(9), 869-875.
[http://dx.doi.org/10.1038/s41558-022-01426-1] [PMID: 35968032]
[3]
Al-Delaimy, A.K. The prospective effects of climate change on neglected tropical diseases in the eastern mediterranean region: A review. Curr. Environ. Health Rep., 2022, 9(2), 315-323.
[http://dx.doi.org/10.1007/s40572-022-00339-7] [PMID: 35286599]
[4]
Ending the neglect to attain the sustainable development goals: A road map for neglected tropical diseases 2021–2030. Available from: https://www.who.int/publications-detail-redirect/9789240010352 (Accessed on: 2023-02-01).
[5]
Sustainable Development Goals | United Nations Development Programme. UNDP. Available from: https://www.undp.org/sustainable-development-goals (Accessed on: 2023-02-01).
[6]
Siqueira-Neto, J.L.; Debnath, A.; McCall, L.I.; Bernatchez, J.A.; Ndao, M.; Reed, S.L.; Rosenthal, P.J. Cysteine proteases in protozoan parasites. PLoS Negl. Trop. Dis., 2018, 12(8), e0006512.
[http://dx.doi.org/10.1371/journal.pntd.0006512] [PMID: 30138453]
[7]
Rawlings, N.D.; Barrett, A.J.; Thomas, P.D.; Huang, X.; Bateman, A.; Finn, R.D. The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database. Nucleic Acids Res., 2018, 46(D1), D624-D632.
[http://dx.doi.org/10.1093/nar/gkx1134] [PMID: 29145643]
[8]
Jílková, A.; Horn, M.; Mareš, M. Structural and functional characterization of schistosoma mansoni cathepsin B1. In: Methods in Molecular Biology; Humana Press Inc., 2020; pp. 145-158.
[http://dx.doi.org/10.1007/978-1-0716-0635-3_12]
[9]
Caffrey, C.R.; Salter, J.P.; Lucas, K.D.; Khiem, D.; Hsieh, I.; Lim, K.C.; Ruppel, A.; McKerrow, J.H.; Sajid, M. SmCB2, a novel tegumental cathepsin B from adult Schistosoma mansoni. Mol. Biochem. Parasitol., 2002, 121(1), 49-61.
[http://dx.doi.org/10.1016/S0166-6851(02)00022-1] [PMID: 11985862]
[10]
Sajid, M.; McKerrow, J.H.; Hansell, E.; Mathieu, M.A.; Lucas, K.D.; Hsieh, I.; Greenbaum, D.; Bogyo, M.; Salter, J.P.; Lim, K.C.; Franklin, C.; Kim, J-H.; Caffrey, C.R. Functional expression and characterization of Schistosoma mansoni cathepsin B and its trans-activation by an endogenous asparaginyl endopeptidase. Mol. Biochem. Parasitol., 2003, 131(1), 65-75.
[http://dx.doi.org/10.1016/S0166-6851(03)00194-4] [PMID: 12967713]
[11]
Jílková, A.; Řezáčová, P.; Lepšík, M.; Horn, M.; Váchová, J.; Fanfrlík, J.; Brynda, J.; McKerrow, J.H.; Caffrey, C.R.; Mareš, M. Structural basis for inhibition of cathepsin B drug target from the human blood fluke, Schistosoma mansoni. J. Biol. Chem., 2011, 286(41), 35770-35781.
[http://dx.doi.org/10.1074/jbc.M111.271304] [PMID: 21832058]
[12]
Colley, D.G.; Bustinduy, A.L.; Secor, W.E.; King, C.H. Human schistosomiasis. Lancet, 2014, 383(9936), 2253-2264.
[http://dx.doi.org/10.1016/S0140-6736(13)61949-2] [PMID: 24698483]
[13]
Caffrey, C.R. Chemotherapy of schistosomiasis: Present and future. Curr. Opin. Chem. Biol., 2007, 11(4), 433-439.
[http://dx.doi.org/10.1016/j.cbpa.2007.05.031] [PMID: 17652008]
[14]
Caffrey, C.R.; Secor, W.E. Schistosomiasis. Curr. Opin. Infect. Dis., 2011, 24(5), 410-417.
[http://dx.doi.org/10.1097/QCO.0b013e328349156f] [PMID: 21734570]
[15]
Thétiot-Laurent, S.A.L.; Boissier, J.; Robert, A.; Meunier, B. Schistosomiasis chemotherapy. Angew. Chem. Int. Ed., 2013, 52(31), 7936-7956.
[http://dx.doi.org/10.1002/anie.201208390] [PMID: 23813602]
[16]
Caffrey, C.R.; El-Sakkary, N.; Mäder, P.; Krieg, R.; Becker, K.; Schlitzer, M.; Drewry, D.H.; Vennerstrom, J.L.; Grevelding, C.G. Drug discovery and development for schistosomiasis. In: Neglected Tropical Diseases; John Wiley & Sons, Ltd, 2019; pp. 187-225.
[http://dx.doi.org/10.1002/9783527808656.ch8]
[17]
Abdulla, M.H.; Lim, K.C.; Sajid, M.; McKerrow, J.H.; Caffrey, C.R. Schistosomiasis mansoni: Novel chemotherapy using a cysteine protease inhibitor. PLoS Med., 2007, 4(1), e14.
[http://dx.doi.org/10.1371/journal.pmed.0040014] [PMID: 17214506]
[18]
Horn, M.; Jílková, A.; Vondrášek, J.; Marešová, L.; Caffrey, C.R.; Mareš, M. Mapping the pro-peptide of the Schistosoma mansoni cathepsin B1 drug target: modulation of inhibition by heparin and design of mimetic inhibitors. ACS Chem. Biol., 2011, 6(6), 609-617.
[http://dx.doi.org/10.1021/cb100411v] [PMID: 21375333]
[19]
Jílková, A.; Horn, M.; Řezáčová, P.; Marešová, L.; Fajtová, P.; Brynda, J.; Vondrášek, J.; McKerrow, J.H.; Caffrey, C.R.; Mareš, M. Activation route of the Schistosoma mansoni cathepsin B1 drug target: structural map with a glycosaminoglycan switch. Structure, 2014, 22(12), 1786-1798.
[http://dx.doi.org/10.1016/j.str.2014.09.015] [PMID: 25456815]
[20]
Jílková, A.; Horn, M.; Fanfrlík, J.; Küppers, J.; Pachl, P.; Řezáčová, P.; Lepšík, M.; Fajtová, P.; Rubešová, P.; Chanová, M.; Caffrey, C.R.; Gütschow, M.; Mareš, M. Azanitrile inhibitors of the SmCB1 protease target are lethal to Schistosoma mansoni: Structural and mechanistic insights into chemotype reactivity. ACS Infect. Dis., 2021, 7(1), 189-201.
[http://dx.doi.org/10.1021/acsinfecdis.0c00644] [PMID: 33301315]
[21]
Jílková, A.; Rubešová, P.; Fanfrlík, J.; Fajtová, P.; Řezáčová, P.; Brynda, J.; Lepšík, M.; Mertlíková-Kaiserová, H.; Emal, C.D.; Renslo, A.R.; Roush, W.R.; Horn, M.; Caffrey, C.R.; Mareš, M. Druggable hot spots in the schistosomiasis cathepsin B1 target identified by functional and binding mode analysis of potent vinyl sulfone inhibitors. ACS Infect. Dis., 2021, 7(5), 1077-1088.
[http://dx.doi.org/10.1021/acsinfecdis.0c00501] [PMID: 33175511]
[22]
Ward, D.J.; Van de Langemheen, H.; Koehne, E.; Kreidenweiss, A.; Liskamp, R.M.J. Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti- parasitic activity against Schistosoma mansoni. Bioorg. Med. Chem., 2019, 27(13), 2857-2870.
[http://dx.doi.org/10.1016/j.bmc.2019.05.014] [PMID: 31126821]
[23]
Nakamura, Y.K.; Matsuo, T.; Shimoi, K.; Nakamura, Y.; Tomita, I. S-methyl methanethiosulfonate, bio-antimutagen in homogenates of Cruciferae and Liliaceae vegetables. Biosci. Biotechnol. Biochem., 1996, 60(9), 1439-1443.
[http://dx.doi.org/10.1271/bbb.60.1439] [PMID: 8987591]
[24]
Rodríguez-Romero, A.; Hernández-Santoyo, A.; del Pozo Yauner, L.; Kornhauser, A.; Fernández-Velasco, D.A. Structure and inactivation of triosephosphate isomerase from Entamoeba histolytica. J. Mol. Biol., 2002, 322(4), 669-675.
[http://dx.doi.org/10.1016/S0022-2836(02)00809-4] [PMID: 12270704]
[25]
Millian, N.S.; Garrow, T.A. Human betaine-homocysteine methyltransferase is a zinc metalloenzyme. Arch. Biochem. Biophys., 1998, 356(1), 93-98.
[http://dx.doi.org/10.1006/abbi.1998.0757] [PMID: 9681996]
[26]
Lowther, W.T.; Brot, N.; Weissbach, H.; Honek, J.F.; Matthews, B.W. Thiol–disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase. Proc. Natl. Acad. Sci., 2000, 97(12), 6463-6468.
[http://dx.doi.org/10.1073/pnas.97.12.6463] [PMID: 10841552]
[27]
Chagas disease. Available from: https://www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis) (Accessed on: 2023-02-01).
[28]
Chagas disease - PAHO/WHO | Pan American Health Organization. Available from: https://www.paho.org/en/topics/chagas-disease (Accessed on: 2023-02-01).
[29]
Symptoms, transmission, and current treatments for Chagas disease | DNDi. Available from: https://dndi.org/diseases/chagas/facts/ (Accessed on: 2023-02-01).
[30]
Engel, J.C.; Doyle, P.S.; Palmer, J.; Hsieh, I.; Bainton, D.F.; McKerrow, J.H. Cysteine protease inhibitors alter Golgi complex ultrastructure and function in Trypanosoma cruzi. J. Cell Sci., 1998, 111(5), 597-606.
[http://dx.doi.org/10.1242/jcs.111.5.597] [PMID: 9454733]
[31]
McKerrow, J.H. Development of cysteine protease inhibitors as chemotherapy for parasitic diseases: insights on safety, target validation, and mechanism of action. Int. J. Parasitol., 1999, 29(6), 833-837.
[http://dx.doi.org/10.1016/S0020-7519(99)00044-2] [PMID: 10480720]
[32]
Cazzulo, J.; Stoka, V.; Turk, V. The major cysteine proteinase of Trypanosoma cruzi: A valid target for chemotherapy of Chagas disease. Curr. Pharm. Des., 2001, 7(12), 1143-1156.
[http://dx.doi.org/10.2174/1381612013397528] [PMID: 11472258]
[33]
Massarico Serafim, R.A.; Gonçalves, J.E.; de Souza, F.P.; de Melo Loureiro, A.P.; Storpirtis, S.; Krogh, R.; Andricopulo, A.D.; Dias, L.C.; Ferreira, E.I. Design, synthesis and biological evaluation of hybrid bioisoster derivatives of N-acylhydrazone and furoxan groups with potential and selective anti-Trypanosoma cruzi activity. Eur. J. Med. Chem., 2014, 82, 418-425.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.077] [PMID: 24929292]
[34]
Ferreira, L.G.; Andricopulo, A.D. Targeting cysteine proteases in trypanosomatid disease drug discovery. Pharmacol. Ther., 2017, 180, 49-61.
[http://dx.doi.org/10.1016/j.pharmthera.2017.06.004] [PMID: 28579388]
[35]
Doyle, P.S.; Zhou, Y.M.; Hsieh, I.; Greenbaum, D.C.; McKerrow, J.H.; Engel, J.C. The Trypanosoma cruzi protease cruzain mediates immune evasion. PLoS Pathog., 2011, 7(9), e1002139.
[http://dx.doi.org/10.1371/journal.ppat.1002139] [PMID: 21909255]
[36]
Ndao, M.; Beaulieu, C.; Black, W.C.; Isabel, E.; Vasquez- Camargo, F.; Nath-Chowdhury, M.; Massé, F.; Mellon, C.; Methot, N.; Nicoll-Griffith, D.A. Reversible cysteine protease inhibitors show promise for a Chagas disease cure. Antimicrob. Agents Chemother., 2014, 58(2), 1167-1178.
[http://dx.doi.org/10.1128/AAC.01855-13] [PMID: 24323474]
[37]
Pauli, I.; Rezende, C.O., Jr; Slafer, B.W.; Dessoy, M.A.; de Souza, M.L.; Ferreira, L.L.G.; Adjanohun, A.L.M.; Ferreira, R.S.; Magalhães, L.G.; Krogh, R.; Michelan-Duarte, S.; Del Pintor, R.V.; da Silva, F.B.R.; Cruz, F.C.; Dias, L.C.; Andricopulo, A.D. Multiparameter optimization of trypanocidal cruzain inhibitors with in vivo activity and favorable pharmacokinetics. Front. Pharmacol., 2022, 12, 774069.
[http://dx.doi.org/10.3389/fphar.2021.774069] [PMID: 35069198]
[38]
Ferreira, R.S.; Simeonov, A.; Jadhav, A.; Eidam, O.; Mott, B.T.; Keiser, M.J.; McKerrow, J.H.; Maloney, D.J.; Irwin, J.J.; Shoichet, B.K. Complementarity between a docking and a high-throughput screen in discovering new cruzain inhibitors. J. Med. Chem., 2010, 53(13), 4891-4905.
[http://dx.doi.org/10.1021/jm100488w] [PMID: 20540517]
[39]
Ferreira, R.S.; Dessoy, M.A.; Pauli, I.; Souza, M.L.; Krogh, R.; Sales, A.I.L.; Oliva, G.; Dias, L.C.; Andricopulo, A.D. Synthesis, biological evaluation, and structure-activity relationships of potent noncovalent and nonpeptidic cruzain inhibitors as anti-Trypanosoma cruzi agents. J. Med. Chem., 2014, 57(6), 2380-2392.
[http://dx.doi.org/10.1021/jm401709b] [PMID: 24533839]
[40]
Kuhn, B.; Mohr, P.; Stahl, M. Intramolecular hydrogen bonding in medicinal chemistry. J. Med. Chem., 2010, 53(6), 2601-2611.
[http://dx.doi.org/10.1021/jm100087s] [PMID: 20175530]
[41]
Libisch, M.G.; Rego, N.; Robello, C. Transcriptional studies on Trypanosoma cruzi – host cell interactions: A complex puzzle of variables. Front. Cell. Infect. Microbiol., 2021, 11, 692134.
[http://dx.doi.org/10.3389/fcimb.2021.692134] [PMID: 34222052]
[42]
Neitz, R.J.; Bryant, C.; Chen, S.; Gut, J.; Hugo Caselli, E.; Ponce, S.; Chowdhury, S.; Xu, H.; Arkin, M.R.; Ellman, J.A.; Renslo, A.R. Tetrafluorophenoxymethyl ketone cruzain inhibitors with improved pharmacokinetic properties as therapeutic leads for Chagas’ disease. Bioorg. Med. Chem. Lett., 2015, 25(21), 4834-4837.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.066] [PMID: 26144347]
[43]
Brak, K.; Kerr, I.D.; Barrett, K.T.; Fuchi, N.; Debnath, M.; Ang, K.; Engel, J.C.; McKerrow, J.H.; Doyle, P.S.; Brinen, L.S.; Ellman, J.A. Nonpeptidic tetrafluorophenoxymethyl ketone cruzain inhibitors as promising new leads for Chagas disease chemotherapy. J. Med. Chem., 2010, 53(4), 1763-1773.
[http://dx.doi.org/10.1021/jm901633v] [PMID: 20088534]
[44]
Jacobsen, W.; Christians, U.; Benet, L.Z. In vitro evaluation of the disposition of a novel cysteine protease inhibitor. Drug Metab. Dispos., 2000, 28(11), 1343-1351.
[PMID: 11038163]
[45]
Tilley, L.; Straimer, J.; Gnädig, N.F.; Ralph, S.A.; Fidock, D.A. Artemisinin action and resistance in Plasmodium falciparum. Trends Parasitol., 2016, 32(9), 682-696.
[http://dx.doi.org/10.1016/j.pt.2016.05.010] [PMID: 27289273]
[46]
Fact sheet about malaria. Available from: https://www.who.int/news-room/fact-sheets/detail/malaria
[47]
Ettari, R.; Bova, F.; Zappalà, M.; Grasso, S.; Micale, N. Falcipain-2 inhibitors. Med. Res. Rev., 2010, 30(1), 136-167.
[http://dx.doi.org/10.1002/med.20163] [PMID: 19526594]
[48]
Bekono, B.D.; Ntie-Kang, F.; Owono Owono, L.C.; Megnassan, E. Targeting cysteine proteases from Plasmodium falciparum: A general overview, rational drug design and computational approaches for drug discovery. Curr. Drug Targets, 2018, 19(5), 501-526.
[http://dx.doi.org/10.2174/1389450117666161221122432] [PMID: 28003005]
[49]
Chen, W.; Huang, Z.; Wang, W.; Mao, F.; Guan, L.; Tang, Y.; Jiang, H.; Li, J.; Huang, J.; Jiang, L.; Zhu, J. Discovery of new antimalarial agents: Second-generation dual inhibitors against FP-2 and PfDHFR via fragments assembely. Bioorg. Med. Chem., 2017, 25(24), 6467-6478.
[http://dx.doi.org/10.1016/j.bmc.2017.10.017] [PMID: 29111368]
[50]
Stoye, A.; Juillard, A.; Tang, A.H.; Legac, J.; Gut, J.; White, K.L.; Charman, S.A.; Rosenthal, P.J.; Grau, G.E.R.; Hunt, N.H.; Payne, R.J. Falcipain inhibitors based on the natural product gallinamide a are potent in vitro and in vivo antimalarials. J. Med. Chem., 2019, 62(11), 5562-5578.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00504] [PMID: 31062592]
[51]
Gresty, K.J.; Gray, K.A.; Bobogare, A.; Wini, L.; Taleo, G.; Hii, J.; Cheng, Q.; Waters, N.C. Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy. Malar. J., 2014, 13(1), 402.
[http://dx.doi.org/10.1186/1475-2875-13-402] [PMID: 25311473]
[52]
Metzger, V.T.; Eun, C.; Kekenes-Huskey, P.M.; Huber, G.; McCammon, J.A. Electrostatic channeling in P. falciparum DHFR-TS: Brownian dynamics and Smoluchowski modeling. Biophys. J., 2014, 107(10), 2394-2402.
[http://dx.doi.org/10.1016/j.bpj.2014.09.039] [PMID: 25418308]
[53]
Barnett, D.S.; Guy, R.K. Antimalarials in development in 2014. Chem. Rev., 2014, 114(22), 11221-11241.
[http://dx.doi.org/10.1021/cr500543f] [PMID: 25340626]
[54]
Lamb, K.M.; G-Dayanandan, N.; Wright, D.L.; Anderson, A.C. Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase. Biochemistry, 2013, 52(41), 7318-7326.
[http://dx.doi.org/10.1021/bi400852h] [PMID: 24053334]
[55]
Huang, H.; Lu, W.; Li, X.; Cong, X.; Ma, H.; Liu, X.; Zhang, Y.; Che, P.; Ma, R.; Li, H.; Shen, X.; Jiang, H.; Huang, J.; Zhu, J. Design and synthesis of small molecular dual inhibitor of falcipain-2 and dihydrofolate reductase as antimalarial agent. Bioorg. Med. Chem. Lett., 2012, 22(2), 958-962.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.011] [PMID: 22192590]
[56]
Conroy, T.; Guo, J.T.; Elias, N.; Cergol, K.M.; Gut, J.; Legac, J.; Khatoon, L.; Liu, Y.; McGowan, S.; Rosenthal, P.J.; Hunt, N.H.; Payne, R.J. Synthesis of gallinamide A analogues as potent falcipain inhibitors and antimalarials. J. Med. Chem., 2014, 57(24), 10557-10563.
[http://dx.doi.org/10.1021/jm501439w] [PMID: 25412465]
[57]
Brun, R.; Blum, J.; Chappuis, F.; Burri, C. Human African trypanosomiasis. Lancet, 2010, 375(9709), 148-159.
[http://dx.doi.org/10.1016/S0140-6736(09)60829-1] [PMID: 19833383]
[58]
Feasey, N.; Wansbrough-Jones, M.; Mabey, D.C.W.; Solomon, A.W. Neglected tropical diseases. Br. Med. Bull., 2010, 93(1), 179-200.
[http://dx.doi.org/10.1093/bmb/ldp046] [PMID: 20007668]
[59]
Malvy, D.; Chappuis, F. Sleeping sickness. Clin. Microbiol. Infect., 2011, 17(7), 986-995.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03536.x] [PMID: 21722252]
[60]
Priotto, G.; Kasparian, S.; Mutombo, W.; Ngouama, D.; Ghorashian, S.; Arnold, U.; Ghabri, S.; Baudin, E.; Buard, V.; Kazadi-Kyanza, S.; Ilunga, M.; Mutangala, W.; Pohlig, G.; Schmid, C.; Karunakara, U.; Torreele, E.; Kande, V. Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: A multicentre, randomised, phase III, non-inferiority trial. Lancet, 2009, 374(9683), 56-64.
[http://dx.doi.org/10.1016/S0140-6736(09)61117-X] [PMID: 19559476]
[61]
Bisser, S.; N’Siesi, F.X.; Lejon, V.; Preux, P.M.; Van Nieuwenhove, S.; Miaka Mia Bilenge, C.; Büscher, P. Equivalence trial of melarsoprol and nifurtimox monotherapy and combination therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping sickness. J. Infect. Dis., 2007, 195(3), 322-329.
[http://dx.doi.org/10.1086/510534] [PMID: 17205469]
[62]
Delespaux, V.; Dekoning, H. Drugs and drug resistance in African trypanosomiasis. Drug Resist. Updat., 2007, 10(1-2), 30-50.
[http://dx.doi.org/10.1016/j.drup.2007.02.004] [PMID: 17409013]
[63]
DNDi – Best science for the most neglected. Available from: https://dndi.org/(Accessed on: 2023-02-01).
[64]
Mesu, V.K.B.K.; Kalonji, W.M.; Bardonneau, C.; Mordt, O.V.; Blesson, S.; Simon, F.; Delhomme, S.; Bernhard, S.; Kuziena, W.; Lubaki, J.P.F.; Vuvu, S.L.; Ngima, P.N.; Mbembo, H.M.; Ilunga, M.; Bonama, A.K.; Heradi, J.A.; Solomo, J.L.L.; Mandula, G.; Badibabi, L.K.; Dama, F.R.; Lukula, P.K.; Tete, D.N.; Lumbala, C.; Scherrer, B.; Strub- Wourgaft, N.; Tarral, A. Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: A pivotal multicentre, randomised, non-inferiority trial. Lancet, 2018, 391(10116), 144-154.
[http://dx.doi.org/10.1016/S0140-6736(17)32758-7] [PMID: 29113731]
[65]
Fexinidazole for T.b. rhodesiense | DNDi. Available from: https://dndi.org/research-development/portfolio/fexinidazole-tb-rhodesiense/ (Accessed on: 2023-02-01).
[66]
Betu Kumeso, V.K.; Kalonji, W.M.; Rembry, S.; Valverde, M.O.; Ngolo, T.D.; Prêtre, A.; Delhomme, S.; Ilunga, W.K.M.; Camara, M.; Catusse, J.; Schneitter, S.; Nusbaumer, M.; Mwamba, M.E.; Mahenzi, M.H.; Makaya, M.J.; Layba, C.M.; Akwaso, M.F.; Kaninda, B.L.; Kasongo, B.A.; Kavunga, L.P.; Mutanda, K.S.; Mariero, P.P.; Mokilifi, N.R.; Embana, M.H.; Asuka, A.N.A.; Kobo, M.V.; Mulenge, N.E.; Fifi, N.B.A.; Scherrer, B.; Strub- Wourgaft, N.; Tarral, A. Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense: A multicentre, open-label, single-arm, phase 2/3 trial. Lancet Infect. Dis., 2023, 23(4), 463-470.
[http://dx.doi.org/10.1016/S1473-3099(22)00660-0] [PMID: 36460027]
[67]
Ettari, R.; Previti, S.; Tamborini, L.; Cullia, G.; Grasso, S.; Zappalà, M. The inhibition of cysteine proteases rhodesain and TbCatB: A valuable approach to treat human African trypanosomiasis. Mini Rev. Med. Chem., 2016, 16(17), 1374-1391.
[http://dx.doi.org/10.2174/1389557515666160509125243] [PMID: 27156518]
[68]
Caffrey, C.R.; Hansell, E.; Lucas, K.D.; Brinen, L.S.; Alvarez Hernandez, A.; Cheng, J.; Gwaltney, S.L., II; Roush, W.R.; Stierhof, Y.D.; Bogyo, M.; Steverding, D.; McKerrow, J.H. Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol. Biochem. Parasitol., 2001, 118(1), 61-73.
[http://dx.doi.org/10.1016/S0166-6851(01)00368-1] [PMID: 11704274]
[69]
Davidbarry, J.; McCulloch, R. Antigenic variation in trypanosomes: Enhanced phenotypic variation in a eukaryotic parasite. Adv. Parasitol., 2001, 49, 1-70.
[http://dx.doi.org/10.1016/S0065-308X(01)49037-3] [PMID: 11461029]
[70]
Overath, P.; Chaudhri, M.; Steverding, D.; Ziegelbauer, K. Invariant surface proteins in bloodstream forms of Trypanosoma brucei. Parasitol. Today, 1994, 10(2), 53-58.
[http://dx.doi.org/10.1016/0169-4758(94)90393-X] [PMID: 15275499]
[71]
Lonsdale-Eccles, J.D.; Grab, D.J. Trypanosome hydrolases and the blood–brain barrier. Trends Parasitol., 2002, 18(1), 17-19.
[http://dx.doi.org/10.1016/S1471-4922(01)02120-1] [PMID: 11850009]
[72]
Abdulla, M.H.; O’Brien, T.; Mackey, Z.B.; Sajid, M.; Grab, D.J.; McKerrow, J.H. RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model. PLoS Negl. Trop. Dis., 2008, 2(9), e298.
[http://dx.doi.org/10.1371/journal.pntd.0000298] [PMID: 18820745]
[73]
Steverding, D.; Sexton, D.W.; Wang, X.; Gehrke, S.S.; Wagner, G.K.; Caffrey, C.R. Trypanosoma brucei: Chemical evidence that cathepsin L is essential for survival and a relevant drug target. Int. J. Parasitol., 2012, 42(5), 481-488.
[http://dx.doi.org/10.1016/j.ijpara.2012.03.009] [PMID: 22549023]
[74]
Kerr, I.D.; Lee, J.H.; Farady, C.J.; Marion, R.; Rickert, M.; Sajid, M.; Pandey, K.C.; Caffrey, C.R.; Legac, J.; Hansell, E.; McKerrow, J.H.; Craik, C.S.; Rosenthal, P.J.; Brinen, L.S. Vinyl sulfones as antiparasitic agents and a structural basis for drug design. J. Biol. Chem., 2009, 284(38), 25697-25703.
[http://dx.doi.org/10.1074/jbc.M109.014340] [PMID: 19620707]
[75]
Kerr, I.D.; Wu, P.; Marion-Tsukamaki, R.; Mackey, Z.B.; Brinen, L.S. Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei. PLoS Negl. Trop. Dis., 2010, 4(6), e701.
[http://dx.doi.org/10.1371/journal.pntd.0000701] [PMID: 20544024]
[76]
Giroud, M.; Kuhn, B.; Saint-Auret, S.; Kuratli, C.; Martin, R.E.; Schuler, F.; Diederich, F.; Kaiser, M.; Brun, R.; Schirmeister, T.; Haap, W. 2 H-1,2,3-triazole-based dipeptidyl nitriles: Potent, selective, and trypanocidal rhodesain inhibitors by structure-based design. J. Med. Chem., 2018, 61(8), 3370-3388.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01870] [PMID: 29590751]
[77]
Giroud, M.; Dietzel, U.; Anselm, L.; Banner, D.; Kuglstatter, A.; Benz, J.; Blanc, J.B.; Gaufreteau, D.; Liu, H.; Lin, X.; Stich, A.; Kuhn, B.; Schuler, F.; Kaiser, M.; Brun, R.; Schirmeister, T.; Kisker, C.; Diederich, F.; Haap, W. Repurposing a library of human cathepsin L ligands: Identification of macrocyclic lactams as potent rhodesain and Trypanosoma brucei inhibitors. J. Med. Chem., 2018, 61(8), 3350-3369.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01869] [PMID: 29590750]
[78]
Eliel, E.L.; Wilen, S.H.; Mander, L.N. Chirality in molecules devoid of chiral centers. University of Pittsburgh, 1994.
[79]
LaPlante, S.R.; Forgione, P.; Boucher, C.; Coulombe, R.; Gillard, J.; Hucke, O.; Jakalian, A.; Joly, M.A.; Kukolj, G.; Lemke, C.; McCollum, R.; Titolo, S.; Beaulieu, P.L.; Stammers, T. Enantiomeric atropisomers inhibit HCV polymerase and/or HIV matrix: characterizing hindered bond rotations and target selectivity. J. Med. Chem., 2014, 57(5), 1944-1951.
[http://dx.doi.org/10.1021/jm401202a] [PMID: 24024973]
[80]
Target product profile for sleeping sickness | DNDi. Available from: https://dndi.org/diseases/sleeping-sickness/target-product-profile/ (Accessed on: 2023-02-01).
[81]
Jung, S.; Fuchs, N.; Johe, P.; Wagner, A.; Diehl, E.; Yuliani, T.; Zimmer, C.; Barthels, F.; Zimmermann, R.A.; Klein, P.; Waigel, W.; Meyr, J.; Opatz, T.; Tenzer, S.; Distler, U.; Räder, H.J.; Kersten, C.; Engels, B.; Hellmich, U.A.; Klein, J.; Schirmeister, T. Fluorovinylsulfones and -sulfonates as potent covalent reversible inhibitors of the trypanosomal cysteine protease rhodesain: Structure–activity relationship, inhibition mechanism, metabolism, and in vivo studies. J. Med. Chem., 2021, 64(16), 12322-12358.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01002] [PMID: 34378914]
[82]
Lee, C.U.; Grossmann, T.N. Reversible covalent inhibition of a protein target. Angew. Chem. Int. Ed., 2012, 51(35), 8699-8700.
[http://dx.doi.org/10.1002/anie.201203341] [PMID: 22806944]
[83]
Lammert, C.; Einarsson, S.; Saha, C.; Niklasson, A.; Bjornsson, E.; Chalasani, N. Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals. Hepatology, 2008, 47(6), 2003-2009.
[http://dx.doi.org/10.1002/hep.22272] [PMID: 18454504]
[84]
Kalgutkar, A.S.; Dalvie, D.K. Drug discovery for a new generation of covalent drugs. Expert Opin. Drug Discov., 2012, 7(7), 561-581.
[http://dx.doi.org/10.1517/17460441.2012.688744] [PMID: 22607458]
[85]
Jung, S.; Fuchs, N.; Grathwol, C.; Hellmich, U.A.; Wagner, A.; Diehl, E.; Willmes, T.; Sotriffer, C.; Schirmeister, T. New peptidomimetic rhodesain inhibitors with improved selectivity towards human cathepsins. Eur. J. Med. Chem., 2022, 238, 114460.
[http://dx.doi.org/10.1016/j.ejmech.2022.114460] [PMID: 35597010]
[86]
Boike, L.; Henning, N.J.; Nomura, D.K. Advances in covalent drug discovery. Nat. Rev. Drug Discov., 2022, 21(12), 881-898.
[http://dx.doi.org/10.1038/s41573-022-00542-z] [PMID: 36008483]
[87]
Serafim, R.A.M.; Haarer, L.; Pedreira, J.G.B.; Gehringer, M. Covalent chemical probes for protein kinases. Curr. Opin. Chem. Biol., 2023, 3, 100040.
[http://dx.doi.org/10.1016/j.crchbi.2022.100040]
[88]
De Vita, E. 10 years into the resurgence of covalent drugs. Future Med. Chem., 2021, 13(2), 193-210.
[http://dx.doi.org/10.4155/fmc-2020-0236] [PMID: 33275063]

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