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Review Article

三十年来针对恶性肿瘤开发抗疟原虫药物:我们学到了什么?下一步可以做什么?

卷 31, 期 16, 2024

发表于: 22 September, 2023

页: [2234 - 2263] 页: 30

弟呕挨: 10.2174/0929867331666230913165219

价格: $65

摘要

疟疾是一种毁灭性的传染病，影响着地球上热带地区的大量人口。它是由疟原虫属的寄生虫引起的，其中恶性疟原虫是该疾病最致命的形式。在人类宿主的红细胞内阶段，疟疾寄生虫利用一系列蛋白酶繁殖和降解血红蛋白(Hb)，其中包括两种半胱氨酸蛋白酶，镰状蛋白酶2和3 (FP-2和FP-3)。由于其作为主要血红蛋白酶的作用，FP-2和FP-3已成为研究的目标，旨在发现新的抗疟药物和许多具有抗这些酶活性的抑制剂，并且已在培养物中发现寄生虫。尽管如此，人类半胱氨酸组织蛋白酶的交叉抑制仍然是这些化合物在临床应用中需要克服的一个严重障碍。在本文中，我们回顾了FP-2/3的主要功能和结构特性，并描述了几十年来在该领域活跃研究中报道的作为这些蛋白酶抑制剂的不同化合物系列。特别注意的是广泛的计算机辅助药物设计(CADD)技术成功地应用于发现新的活性化合物。最后，我们提供了指导方针，在我们的理解中，这将有助于促进新的FP-2/3抑制剂的合理发现。

关键词: 恶性疟原虫2，恶性疟原虫3，恶性疟原虫，疟疾，药物发现，抑制剂。

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[1]
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]
[2]
Teixeira, C.; Gomes, J.R.; Gomes, P. Falcipains, Plasmodium falciparum cysteine proteases as key drug targets against malaria. Curr. Med. Chem., 2011, 18(10), 1555-1572.
[http://dx.doi.org/10.2174/092986711795328328] [PMID: 21428877]
[3]
Rosenthal, P.J. Falcipain cysteine proteases of malaria parasites: An update. Biochim. Biophys. Acta. Proteins Proteomics, 2020, 1868(3), 140362.
[http://dx.doi.org/10.1016/j.bbapap.2020.140362] [PMID: 31927030]
[4]
World malaria report. 2022. Available From: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022 (Accessed on March 27th 2023).
[5]
Zhu, L.; van der Pluijm, R.W.; Kucharski, M.; Nayak, S.; Tripathi, J.; White, N.J.; Day, N.P.J.; Faiz, A.; Phyo, A.P.; Amaratunga, C.; Lek, D.; Ashley, E.A.; Nosten, F.; Smithuis, F.; Ginsburg, H.; von Seidlein, L.; Lin, K.; Imwong, M.; Chotivanich, K.; Mayxay, M.; Dhorda, M.; Nguyen, H.C.; Nguyen, T.N.T.; Miotto, O.; Newton, P.N.; Jittamala, P.; Tripura, R.; Pukrittayakamee, S.; Peto, T.J.; Hien, T.T.; Dondorp, A.M.; Bozdech, Z. Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response. Commun. Biol., 2022, 5(1), 274.
[http://dx.doi.org/10.1038/s42003-022-03215-0] [PMID: 35347215]
[6]
Ashley, E.A.; Dhorda, M.; Fairhurst, R.M.; Amaratunga, C.; Lim, P.; Suon, S.; Sreng, S.; Anderson, J.M.; Mao, S.; Sam, B.; Sopha, C.; Chuor, C.M.; Nguon, C.; Sovannaroth, S.; Pukrittayakamee, S.; Jittamala, P.; Chotivanich, K.; Chutasmit, K.; Suchatsoonthorn, C.; Runcharoen, R.; Hien, T.T.; Thuy-Nhien, N.T.; Thanh, N.V.; Phu, N.H.; Htut, Y.; Han, K.T.; Aye, K.H.; Mokuolu, O.A.; Olaosebikan, R.R.; Folaranmi, O.O.; Mayxay, M.; Khanthavong, M.; Hongvanthong, B.; Newton, P.N.; Onyamboko, M.A.; Fanello, C.I.; Tshefu, A.K.; Mishra, N.; Valecha, N.; Phyo, A.P.; Nosten, F.; Yi, P.; Tripura, R.; Borrmann, S.; Bashraheil, M.; Peshu, J.; Faiz, M.A.; Ghose, A.; Hossain, M.A.; Samad, R.; Rahman, M.R.; Hasan, M.M.; Islam, A.; Miotto, O.; Amato, R.; MacInnis, B.; Stalker, J.; Kwiatkowski, D.P.; Bozdech, Z.; Jeeyapant, A.; Cheah, P.Y.; Sakulthaew, T.; Chalk, J.; Intharabut, B.; Silamut, K.; Lee, S.J.; Vihokhern, B.; Kunasol, C.; Imwong, M.; Tarning, J.; Taylor, W.J.; Yeung, S.; Woodrow, C.J.; Flegg, J.A.; Das, D.; Smith, J.; Venkatesan, M.; Plowe, C.V.; Stepniewska, K.; Guerin, P.J.; Dondorp, A.M.; Day, N.P.; White, N.J. Spread of artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med., 2014, 371(5), 411-423.
[http://dx.doi.org/10.1056/NEJMoa1314981] [PMID: 25075834]
[7]
van der Pluijm, R.W.; Imwong, M.; Chau, N.H.; Hoa, N.T.; Thuy-Nhien, N.T.; Thanh, N.V.; Jittamala, P.; Hanboonkunupakarn, B.; Chutasmit, K.; Saelow, C.; Runjarern, R.; Kaewmok, W.; Tripura, R.; Peto, T.J.; Yok, S.; Suon, S.; Sreng, S.; Mao, S.; Oun, S.; Yen, S.; Amaratunga, C.; Lek, D.; Huy, R.; Dhorda, M.; Chotivanich, K.; Ashley, E.A.; Mukaka, M.; Waithira, N.; Cheah, P.Y.; Maude, R.J.; Amato, R.; Pearson, R.D.; Gonçalves, S.; Jacob, C.G.; Hamilton, W.L.; Fairhurst, R.M.; Tarning, J.; Winterberg, M.; Kwiatkowski, D.P.; Pukrittayakamee, S.; Hien, T.T.; Day, N.P.J.; Miotto, O.; White, N.J.; Dondorp, A.M. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: A prospective clinical, pharmacological, and genetic study. Lancet Infect. Dis., 2019, 19(9), 952-961.
[http://dx.doi.org/10.1016/S1473-3099(19)30391-3] [PMID: 31345710]
[8]
Laurens, M.B. RTS,S/AS01 vaccine (Mosquirix™): An overview. Hum. Vaccin. Immunother., 2020, 16(3), 480-489.
[http://dx.doi.org/10.1080/21645515.2019.1669415] [PMID: 31545128]
[9]
World malaria report. 2021. Available From: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2021 (Accessed on March 27th 2023).
[10]
Silal, S.P. Seasonal targeting of the RTS,S/AS01 malaria vaccine: A complementary tool but sustained funding is required. Lancet Glob. Health, 2022, 10(12), e1693-e1694.
[http://dx.doi.org/10.1016/S2214-109X(22)00477-6] [PMID: 36400073]
[11]
Rosenthal, P.J. Falcipains and other cysteine proteases of malaria parasites. Adv. Exp. Med. Biol., 2011, 712, 30-48.
[http://dx.doi.org/10.1007/978-1-4419-8414-2_3] [PMID: 21660657]
[12]
Roy, K.K. Targeting the active sites of malarial proteases for antimalarial drug discovery: Approaches, progress and challenges. Int. J. Antimicrob. Agents, 2017, 50(3), 287-302.
[http://dx.doi.org/10.1016/j.ijantimicag.2017.04.006] [PMID: 28668681]
[13]
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]
[14]
Ettari, R.; Previti, S.; Di Chio, C.; Zappalà, M. Falcipain-2 and falcipain-3 inhibitors as promising antimalarial agents. Curr. Med. Chem., 2021, 28(15), 3010-3031.
[http://dx.doi.org/10.2174/1875533XMTA4nNzUc3] [PMID: 32744954]
[15]
Marco, M.; Miguel Coteron, J. Falcipain inhibition as a promising antimalarial target. Curr. Top. Med. Chem., 2012, 12(5), 408-444.
[http://dx.doi.org/10.2174/156802612799362913] [PMID: 22242849]
[16]
Khan, S.M.; Waters, A.P. Malaria parasite transmission stages: An update. Trends Parasitol., 2004, 20(12), 575-580.
[http://dx.doi.org/10.1016/j.pt.2004.10.001] [PMID: 15522667]
[17]
Dimopoulos, G.; Kafatos, F.C.; Waters, A.P.; Sinden, R.E. Malaria parasites and the anopheles mosquito. Chem. Immunol., 2002, 80, 27-49.
[http://dx.doi.org/10.1159/000058838] [PMID: 12058645]
[18]
Kappe, S.H.I.; Kaiser, K.; Matuschewski, K. The Plasmodium sporozoite journey: A rite of passage. Trends Parasitol., 2003, 19(3), 135-143.
[http://dx.doi.org/10.1016/S1471-4922(03)00007-2] [PMID: 12643997]
[19]
Wells, T.N.C.; van Huijsduijnen, R.H.; Van Voorhis, W.C. Malaria medicines: A glass half full? Nat. Rev. Drug Discov., 2015, 14(6), 424-442.
[http://dx.doi.org/10.1038/nrd4573] [PMID: 26000721]
[20]
Rosenthal, P.J.; McKerrow, J.H.; Aikawa, M.; Nagasawa, H.; Leech, J.H. A malarial cysteine proteinase is necessary for hemoglobin degradation by Plasmodium falciparum. J. Clin. Invest., 1988, 82(5), 1560-1566.
[http://dx.doi.org/10.1172/JCI113766] [PMID: 3053784]
[21]
Rosenthal, P.J.; Nelson, R.G. Isolation and characterization of a cysteine proteinase gene of Plasmodium falciparum. Mol. Biochem. Parasitol., 1992, 51(1), 143-152.
[http://dx.doi.org/10.1016/0166-6851(92)90209-3] [PMID: 1565129]
[22]
Shenai, B.R.; Sijwali, P.S.; Singh, A.; Rosenthal, P.J. Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. J. Biol. Chem., 2000, 275(37), 29000-29010.
[http://dx.doi.org/10.1074/jbc.M004459200] [PMID: 10887194]
[23]
Sijwali, P.S.; Shenai, B.R.; Gut, J.; Singh, A.; Rosenthal, P.J. Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3. Biochem. J., 2001, 360(2), 481-489.
[http://dx.doi.org/10.1042/bj3600481] [PMID: 11716777]
[24]
Singh, N.; Sijwali, P.S.; Pandey, K.C.; Rosenthal, P.J. Plasmodium falciparum: Biochemical characterization of the cysteine protease falcipain-2′. Exp. Parasitol., 2006, 112(3), 187-192.
[http://dx.doi.org/10.1016/j.exppara.2005.10.007] [PMID: 16337629]
[25]
Sijwali, P.S.; Kato, K.; Seydel, K.B.; Gut, J.; Lehman, J.; Klemba, M.; Goldberg, D.E.; Miller, L.H.; Rosenthal, P.J. Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites. Proc. Natl. Acad. Sci. USA, 2004, 101(23), 8721-8726.
[http://dx.doi.org/10.1073/pnas.0402738101] [PMID: 15166288]
[26]
Eksi, S.; Czesny, B.; Greenbaum, D.C.; Bogyo, M.; Williamson, K.C. Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth. Mol. Microbiol., 2004, 53(1), 243-250.
[http://dx.doi.org/10.1111/j.1365-2958.2004.04108.x] [PMID: 15225318]
[27]
Sijwali, P.S.; Koo, J.; Singh, N.; Rosenthal, P.J. Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum. Mol. Biochem. Parasitol., 2006, 150(1), 96-106.
[http://dx.doi.org/10.1016/j.molbiopara.2006.06.013] [PMID: 16890302]
[28]
Gluzman, I.Y.; Francis, S.E.; Oksman, A.; Smith, C.E.; Duffin, K.L.; Goldberg, D.E. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Invest., 1994, 93(4), 1602-1608.
[http://dx.doi.org/10.1172/JCI117140] [PMID: 8163662]
[29]
Banerjee, R.; Liu, J.; Beatty, W.; Pelosof, L.; Klemba, M.; Goldberg, D.E. Four plasmepsins are active in the Plasmodium falciparum food vacuole, including a protease with an active-site histidine. Proc. Natl. Acad. Sci. USA, 2002, 99(2), 990-995.
[http://dx.doi.org/10.1073/pnas.022630099] [PMID: 11782538]
[30]
Eggleson, K.K.; Duffin, K.L.; Goldberg, D.E. Identification and characterization of falcilysin, a metallopeptidase involved in hemoglobin catabolism within the malaria parasite Plasmodium falciparum. J. Biol. Chem., 1999, 274(45), 32411-32417.
[http://dx.doi.org/10.1074/jbc.274.45.32411] [PMID: 10542284]
[31]
Klemba, M.; Gluzman, I.; Goldberg, D.E. A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation. J. Biol. Chem., 2004, 279(41), 43000-43007.
[http://dx.doi.org/10.1074/jbc.M408123200] [PMID: 15304495]
[32]
Rosenthal, P.J. Plasmodium falciparum: Effects of proteinase inhibitors on globin hydrolysis by cultured malaria parasites. Exp. Parasitol., 1995, 80(2), 272-281.
[http://dx.doi.org/10.1006/expr.1995.1033] [PMID: 7895837]
[33]
Omara-Opyene, A.L.; Moura, P.A.; Sulsona, C.R.; Bonilla, J.A.; Yowell, C.A.; Fujioka, H.; Fidock, D.A.; Dame, J.B. Genetic disruption of the Plasmodium falciparum digestive vacuole plasmepsins demonstrates their functional redundancy. J. Biol. Chem., 2004, 279(52), 54088-54096.
[http://dx.doi.org/10.1074/jbc.M409605200] [PMID: 15491999]
[34]
Subramanian, S.; Hardt, M.; Choe, Y.; Niles, R.K.; Johansen, E.B.; Legac, J.; Gut, J.; Kerr, I.D.; Craik, C.S.; Rosenthal, P.J. Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3. PLoS One, 2009, 4(4), e5156.
[http://dx.doi.org/10.1371/journal.pone.0005156] [PMID: 19357776]
[35]
Rosenthal, P.J.; Wollish, W.S.; Palmer, J.T.; Rasnick, D. Antimalarial effects of peptide inhibitors of a Plasmodium falciparum cysteine proteinase. J. Clin. Invest., 1991, 88(5), 1467-1472.
[http://dx.doi.org/10.1172/JCI115456] [PMID: 1939639]
[36]
Sijwali, P.S.; Rosenthal, P.J. Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proc. Natl. Acad. Sci. USA, 2004, 101(13), 4384-4389.
[http://dx.doi.org/10.1073/pnas.0307720101] [PMID: 15070727]
[37]
Hanspal, M.; Dua, M.; Takakuwa, Y.; Chishti, A.H.; Mizuno, A. Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development. Blood, 2002, 100(3), 1048-1054.
[http://dx.doi.org/10.1182/blood-2002-01-0101] [PMID: 12130521]
[38]
Drew, M.E.; Banerjee, R.; Uffman, E.W.; Gilbertson, S.; Rosenthal, P.J.; Goldberg, D.E. Plasmodium food vacuole plasmepsins are activated by falcipains. J. Biol. Chem., 2008, 283(19), 12870-12876.
[http://dx.doi.org/10.1074/jbc.M708949200] [PMID: 18308731]
[39]
Wang, S.X.; Pandey, K.C.; Somoza, J.R.; Sijwali, P.S.; Kortemme, T.; Brinen, L.S.; Fletterick, R.J.; Rosenthal, P.J.; McKerrow, J.H. Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc. Natl. Acad. Sci., 2006, 103(31), 11503-11508.
[http://dx.doi.org/10.1073/pnas.0600489103] [PMID: 16864794]
[40]
Hogg, T.; Nagarajan, K.; Herzberg, S.; Chen, L.; Shen, X.; Jiang, H.; Wecke, M.; Blohmke, C.; Hilgenfeld, R.; Schmidt, C.L. Structural and functional characterization of Falcipain-2, a hemoglobinase from the malarial parasite Plasmodium falciparum. J. Biol. Chem., 2006, 281(35), 25425-25437.
[http://dx.doi.org/10.1074/jbc.M603776200] [PMID: 16777845]
[41]
Kerr, I.D.; Lee, J.H.; Pandey, K.C.; Harrison, A.; Sajid, M.; Rosenthal, P.J.; Brinen, L.S. Structures of falcipain-2 and falcipain-3 bound to small molecule inhibitors: Implications for substrate specificity. J. Med. Chem., 2009, 52(3), 852-857.
[http://dx.doi.org/10.1021/jm8013663] [PMID: 19128015]
[42]
Chakraborty, S.; Alam, B.; Biswas, S. New insights of falcipain 2 structure from Plasmodium falciparum 3D7 strain. Biochem. Biophys. Res. Commun., 2022, 590, 145-151.
[http://dx.doi.org/10.1016/j.bbrc.2021.12.080] [PMID: 34974303]
[43]
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]
[44]
Machin, J.M.; Kantsadi, A.L.; Vakonakis, I. The complex of Plasmodium falciparum falcipain-2 protease with an (E)-chalcone-based inhibitor highlights a novel, small, molecule-binding site. Malar. J., 2019, 18(1), 388.
[http://dx.doi.org/10.1186/s12936-019-3043-0] [PMID: 31791339]
[45]
Wang, S.X.; Pandey, K.C.; Scharfstein, J.; Whisstock, J.; Huang, R.K.; Jacobelli, J.; Fletterick, R.J.; Rosenthal, P.J.; Abrahamson, M.; Brinen, L.S.; Rossi, A.; Sali, A.; McKerrow, J.H. The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure, 2007, 15(5), 535-543.
[http://dx.doi.org/10.1016/j.str.2007.03.012] [PMID: 17502099]
[46]
Hansen, G.; Heitmann, A.; Witt, T.; Li, H.; Jiang, H.; Shen, X.; Heussler, V.T.; Rennenberg, A.; Hilgenfeld, R. Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium. Structure, 2011, 19(7), 919-929.
[http://dx.doi.org/10.1016/j.str.2011.03.025] [PMID: 21742259]
[47]
Pandey, K.C.; Sijwali, P.S.; Singh, A.; Na, B.K.; Rosenthal, P.J. Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2. J. Biol. Chem., 2004, 279(5), 3484-3491.
[http://dx.doi.org/10.1074/jbc.M310536200] [PMID: 14625277]
[48]
Pandey, K.C.; Wang, S.X.; Sijwali, P.S.; Lau, A.L.; McKerrow, J.H.; Rosenthal, P.J. The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proc. Natl. Acad. Sci. USA, 2005, 102(26), 9138-9143.
[http://dx.doi.org/10.1073/pnas.0502368102] [PMID: 15964982]
[49]
Cotrin, S.S.; Gouvêa, I.E.; Melo, P.M.S.; Bagnaresi, P.; Assis, D.M.; Araújo, M.S.; Juliano, M.A.; Gazarini, M.L.; Rosenthal, P.J.; Juliano, L.; Carmona, A.K. Substrate specificity studies of the cysteine peptidases falcipain-2 and falcipain-3 from Plasmodium falciparum and demonstration of their kininogenase activity. Mol. Biochem. Parasitol., 2013, 187(2), 111-116.
[http://dx.doi.org/10.1016/j.molbiopara.2013.01.002] [PMID: 23354130]
[50]
Rzychon, M.; Chmiel, D.; Stec-Niemczyk, J. Modes of inhibition of cysteine proteases. Acta Biochim. Pol., 2004, 51(4), 861-873.
[PMID: 15625558]
[51]
Powers, J.C.; Asgian, J.L.; Ekici, Ö.D.; James, K.E. Irreversible inhibitors of serine, cysteine, and threonine proteases. Chem. Rev., 2002, 102(12), 4639-4750.
[http://dx.doi.org/10.1021/cr010182v] [PMID: 12475205]
[52]
Ring, C.S.; Sun, E.; McKerrow, J.H.; Lee, G.K.; Rosenthal, P.J.; Kuntz, I.D.; Cohen, F.E. Structure-based inhibitor design by using protein models for the development of antiparasitic agents. Proc. Natl. Acad. Sci. USA, 1993, 90(8), 3583-3587.
[http://dx.doi.org/10.1073/pnas.90.8.3583] [PMID: 8475107]
[53]
Li, R.; Chen, X.; Gong, B.; Selzer, P.M.; Li, Z.; Davidson, E.; Kurzban, G.; Miller, R.E.; Nuzum, E.O.; McKerrow, J.H.; Fletterick, R.J.; Gillmor, S.A.; Craik, C.S.; Kuntz, I.D.; Cohen, F.E.; Kenyon, G.L. Structure-based design of parasitic protease inhibitors. Bioorg. Med. Chem., 1996, 4(9), 1421-1427.
[http://dx.doi.org/10.1016/0968-0896(96)00136-8] [PMID: 8894100]
[54]
Rosenthal, P.J.; Olson, J.E.; Lee, G.K.; Palmer, J.T.; Klaus, J.L.; Rasnick, D. Antimalarial effects of vinyl sulfone cysteine proteinase inhibitors. Antimicrob. Agents Chemother., 1996, 40(7), 1600-1603.
[http://dx.doi.org/10.1128/AAC.40.7.1600] [PMID: 8807047]
[55]
Rosenthal, P.J.; Lee, G.K.; Smith, R.E. Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. J. Clin. Invest., 1993, 91(3), 1052-1056.
[http://dx.doi.org/10.1172/JCI116262] [PMID: 8450035]
[56]
Gamboa de Domínguez, N.D.; Rosenthal, P.J. Cysteine proteinase inhibitors block early steps in hemoglobin degradation by cultured malaria parasites. Blood, 1996, 87(10), 4448-4454.
[http://dx.doi.org/10.1182/blood.V87.10.4448.bloodjournal87104448] [PMID: 8639807]
[57]
Mane, U.R.; Gupta, R.C.; Nadkarni, S.S.; Giridhar, R.R.; Naik, P.P.; Yadav, M.R. Falcipain inhibitors as potential therapeutics for resistant strains of malaria: A patent review. Expert Opin. Ther. Pat., 2013, 23(2), 165-187.
[http://dx.doi.org/10.1517/13543776.2013.743992] [PMID: 23228154]
[58]
Cianni, L.; Feldmann, C.W.; Gilberg, E.; Gütschow, M.; Juliano, L.; Leitão, A.; Bajorath, J.; Montanari, C.A. Can cysteine protease cross-class inhibitors achieve selectivity? J. Med. Chem., 2019, 62(23), 10497-10525.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00683] [PMID: 31361135]
[59]
Citarella, A.; Micale, N. Peptidyl fluoromethyl ketones and their applications in medicinal chemistry. Molecules, 2020, 25(17), 4031.
[http://dx.doi.org/10.3390/molecules25174031] [PMID: 32899354]
[60]
Kato, D.; Boatright, K.M.; Berger, A.B.; Nazif, T.; Blum, G.; Ryan, C.; Chehade, K.A.H.; Salvesen, G.S.; Bogyo, M. Activity-based probes that target diverse cysteine protease families. Nat. Chem. Biol., 2005, 1(1), 33-38.
[http://dx.doi.org/10.1038/nchembio707] [PMID: 16407991]
[61]
Sajid, M.; Robertson, S.A.; Brinen, L.S.; McKerrow, J.H. Cruzain. Adv. Exp. Med. Biol., 2011, 712, 100-115.
[http://dx.doi.org/10.1007/978-1-4419-8414-2_7] [PMID: 21660661]
[62]
Dunny, E.; Evans, P. Vinyl sulfone containing parasitic cysteinyl protease inhibitors. Curr. Bioact. Compd., 2011, 7(4), 218-236.
[http://dx.doi.org/10.2174/157340711798375859]
[63]
Shenai, B.R.; Lee, B.J.; Alvarez-Hernandez, A.; Chong, P.Y.; Emal, C.D.; Neitz, R.J.; Roush, W.R.; Rosenthal, P.J. Structure-activity relationships for inhibition of cysteine protease activity and development of Plasmodium falciparum by peptidyl vinyl sulfones. Antimicrob. Agents Chemother., 2003, 47(1), 154-160.
[http://dx.doi.org/10.1128/AAC.47.1.154-160.2003] [PMID: 12499184]
[64]
Aratikatla, E.K.; Kalamuddin, M.; Malhotra, P.; Mohmmed, A.; Bhattacharya, A.K. Enantioselective synthesis of γ-phenyl-γ-amino vinyl phosphonates and sulfones and their application to the synthesis of novel highly potent antimalarials. ACS Omega, 2020, 5(45), 29025-29037.
[http://dx.doi.org/10.1021/acsomega.0c03470] [PMID: 33225134]
[65]
Shokhen, M.; Khazanov, N.; Albeck, A. The mechanism of papain inhibition by peptidyl aldehydes. Proteins, 2011, 79(3), 975-985.
[http://dx.doi.org/10.1002/prot.22939] [PMID: 21181719]
[66]
Smith, R.A.; Copp, L.J.; Donnelly, S.L.; Spencer, R.W.; Krantz, A. Inhibition of cathepsin B by peptidyl aldehydes and ketones: Slow-binding behavior of a trifluoromethyl ketone. Biochemistry, 1988, 27(17), 6568-6573.
[http://dx.doi.org/10.1021/bi00417a056] [PMID: 3219354]
[67]
Ma, Y.; Yang, K.S.; Geng, Z.Z.; Alugubelli, Y.R.; Shaabani, N.; Vatansever, E.C.; Ma, X.R.; Cho, C.C.; Khatua, K.; Xiao, J.; Blankenship, L.R.; Yu, G.; Sankaran, B.; Li, P.; Allen, R.; Ji, H.; Xu, S.; Liu, W.R. A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals. Eur. J. Med. Chem., 2022, 240, 114570.
[http://dx.doi.org/10.1016/j.ejmech.2022.114570] [PMID: 35779291]
[68]
Lee, B.J.; Singh, A.; Chiang, P.; Kemp, S.J.; Goldman, E.A.; Weinhouse, M.I.; Vlasuk, G.P.; Rosenthal, P.J. Antimalarial activities of novel synthetic cysteine protease inhibitors. Antimicrob. Agents Chemother., 2003, 47(12), 3810-3814.
[http://dx.doi.org/10.1128/AAC.47.12.3810-3814.2003] [PMID: 14638488]
[69]
Ehmke, V.; Kilchmann, F.; Heindl, C.; Cui, K.; Huang, J.; Schirmeister, T.; Diederich, F. Peptidomimetic nitriles as selective inhibitors for the malarial cysteine protease falcipain-2. MedChemComm, 2011, 2(8), 800-804.
[http://dx.doi.org/10.1039/c1md00115a]
[70]
Gauthier, J.Y.; Chauret, N.; Cromlish, W.; Desmarais, S.; Duong, L.T.; Falgueyret, J.P.; Kimmel, D.B.; Lamontagne, S.; Léger, S.; LeRiche, T.; Li, C.S.; Massé, F.; McKay, D.J.; Nicoll-Griffith, D.A.; Oballa, R.M.; Palmer, J.T.; Percival, M.D.; Riendeau, D.; Robichaud, J.; Rodan, G.A.; Rodan, S.B.; Seto, C.; Thérien, M.; Truong, V.L.; Venuti, M.C.; Wesolowski, G.; Young, R.N.; Zamboni, R.; Black, W.C. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg. Med. Chem. Lett., 2008, 18(3), 923-928.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.047] [PMID: 18226527]
[71]
Oballa, R.M.; Truchon, J.F.; Bayly, C.I.; Chauret, N.; Day, S.; Crane, S.; Berthelette, C. A generally applicable method for assessing the electrophilicity and reactivity of diverse nitrile-containing compounds. Bioorg. Med. Chem. Lett., 2007, 17(4), 998-1002.
[http://dx.doi.org/10.1016/j.bmcl.2006.11.044] [PMID: 17157022]
[72]
Ang, K.K.H.; Ratnam, J.; Gut, J.; Legac, J.; Hansell, E.; Mackey, Z.B.; Skrzypczynska, K.M.; Debnath, A.; Engel, J.C.; Rosenthal, P.J.; McKerrow, J.H.; Arkin, M.R.; Renslo, A.R. Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl. Trop. Dis., 2011, 5(5), e1023.
[http://dx.doi.org/10.1371/journal.pntd.0001023] [PMID: 21572521]
[73]
Coterón, J.M.; Catterick, D.; Castro, J.; Chaparro, M.J.; Díaz, B.; Fernández, E.; Ferrer, S.; Gamo, F.J.; Gordo, M.; Gut, J.; de las Heras, L.; Legac, J.; Marco, M.; Miguel, J.; Muñoz, V.; Porras, E.; de la Rosa, J.C.; Ruiz, J.R.; Sandoval, E.; Ventosa, P.; Rosenthal, P.J.; Fiandor, J.M. Falcipain inhibitors: Optimization studies of the 2-pyrimidinecarbonitrile lead series. J. Med. Chem., 2010, 53(16), 6129-6152.
[http://dx.doi.org/10.1021/jm100556b] [PMID: 20672841]
[74]
Nizi, E.; Sferrazza, A.; Fabbrini, D.; Nardi, V.; Andreini, M.; Graziani, R.; Gennari, N.; Bresciani, A.; Paonessa, G.; Harper, S. Peptidomimetic nitrile inhibitors of malarial protease falcipain-2 with high selectivity against human cathepsins. Bioorg. Med. Chem. Lett., 2018, 28(9), 1540-1544.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.069] [PMID: 29615344]
[75]
Chakka, S.K.; Kalamuddin, M.; Sundararaman, S.; Wei, L.; Mundra, S.; Mahesh, R.; Malhotra, P.; Mohmmed, A.; Kotra, L.P. Identification of novel class of falcipain-2 inhibitors as potential antimalarial agents. Bioorg. Med. Chem., 2015, 23(9), 2221-2240.
[http://dx.doi.org/10.1016/j.bmc.2015.02.062] [PMID: 25840796]
[76]
Hernández González, J.E.; Hernández Alvarez, L.; Pascutti, P.G.; Valiente, P.A. Predicting binding modes of reversible peptide-based inhibitors of falcipain-2 consistent with structure-activity relationships. Proteins, 2017, 85(9), 1666-1683.
[http://dx.doi.org/10.1002/prot.25322] [PMID: 28543724]
[77]
Royo, S.; Schirmeister, T.; Kaiser, M.; Jung, S.; Rodríguez, S.; Bautista, J.M.; González, F.V. Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates. Bioorg. Med. Chem., 2018, 26(16), 4624-4634.
[http://dx.doi.org/10.1016/j.bmc.2018.07.015] [PMID: 30037754]
[78]
Linington, R.G.; Clark, B.R.; Trimble, E.E.; Almanza, A.; Ureña, L.D.; Kyle, D.E.; Gerwick, W.H. Antimalarial peptides from marine cyanobacteria: Isolation and structural elucidation of gallinamide A. J. Nat. Prod., 2009, 72(1), 14-17.
[http://dx.doi.org/10.1021/np8003529] [PMID: 19161344]
[79]
Stolze, S.C.; Deu, E.; Kaschani, F.; Li, N.; Florea, B.I.; Richau, K.H.; Colby, T.; van der Hoorn, R.A.L.; Overkleeft, H.S.; Bogyo, M.; Kaiser, M. The antimalarial natural product symplostatin 4 is a nanomolar inhibitor of the food vacuole falcipains. Chem. Biol., 2012, 19(12), 1546-1555.
[http://dx.doi.org/10.1016/j.chembiol.2012.09.020] [PMID: 23261598]
[80]
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]
[81]
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]
[82]
Aratikatla, E.K.; Kalamuddin, M.; Rana, K.C.; Datta, G.; Asad, M.; Sundararaman, S.; Malhotra, P.; Mohmmed, A.; Bhattacharya, A.K. Combating multi-drug resistant malaria parasite by inhibiting falcipain-2 and heme-polymerization: Artemisinin-peptidyl vinyl phosphonate hybrid molecules as new antimalarials. Eur. J. Med. Chem., 2021, 220, 113454.
[http://dx.doi.org/10.1016/j.ejmech.2021.113454] [PMID: 33901900]
[83]
Schulz, F.; Gelhaus, C.; Degel, B.; Vicik, R.; Heppner, S.; Breuning, A.; Leippe, M.; Gut, J.; Rosenthal, P.J.; Schirmeister, T. Screening of protease inhibitors as antiplasmodial agents. Part I: Aziridines and epoxides. ChemMedChem, 2007, 2(8), 1214-1224.
[http://dx.doi.org/10.1002/cmdc.200700070] [PMID: 17562535]
[84]
Li Petri, G.; Di Martino, S.; De Rosa, M. Peptidomimetics: An overview of recent medicinal chemistry efforts toward the discovery of novel small molecule inhibitors. J. Med. Chem., 2022, 65(11), 7438-7475.
[http://dx.doi.org/10.1021/acs.jmedchem.2c00123] [PMID: 35604326]
[85]
Micale, N.; Kozikowski, A.P.; Ettari, R.; Grasso, S.; Zappalà, M.; Jeong, J.J.; Kumar, A.; Hanspal, M.; Chishti, A.H. Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents. J. Med. Chem., 2006, 49(11), 3064-3067.
[http://dx.doi.org/10.1021/jm060405f] [PMID: 16722625]
[86]
Ettari, R.; Nizi, E.; Di Francesco, M.E.; Dude, M.A.; Pradel, G.; Vičík, R.; Schirmeister, T.; Micale, N.; Grasso, S.; Zappalà, M. Development of peptidomimetics with a vinyl sulfone warhead as irreversible falcipain-2 inhibitors. J. Med. Chem., 2008, 51(4), 988-996.
[http://dx.doi.org/10.1021/jm701141u] [PMID: 18232656]
[87]
Ettari, R.; Nizi, E.; Di Francesco, M.E.; Micale, N.; Grasso, S.; Zappalà, M.; Vičík, R.; Schirmeister, T. Nonpeptidic vinyl and allyl phosphonates as falcipain-2 inhibitors. ChemMedChem, 2008, 3(7), 1030-1033.
[http://dx.doi.org/10.1002/cmdc.200800050] [PMID: 18428116]
[88]
Ettari, R.; Micale, N.; Schirmeister, T.; Gelhaus, C.; Leippe, M.; Nizi, E.; Di Francesco, M.E.; Grasso, S.; Zappalà, M. Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors. J. Med. Chem., 2009, 52(7), 2157-2160.
[http://dx.doi.org/10.1021/jm900047j] [PMID: 19296600]
[89]
Ettari, R.; Pinto, A.; Tamborini, L.; Angelo, I.C.; Grasso, S.; Zappalà, M.; Capodicasa, N.; Yzeiraj, L.; Gruber, E.; Aminake, M.N.; Pradel, G.; Schirmeister, T.; De Micheli, C.; Conti, P. Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold as antiprotozoal agents. ChemMedChem, 2014, 9(8)
[http://dx.doi.org/10.1002/cmdc.201402079] [PMID: 24919925]
[90]
Verissimo, E.; Berry, N.; Gibbons, P.; Cristiano, M.L.S.; Rosenthal, P.J.; Gut, J.; Ward, S.A.; O’Neill, P.M. Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(14), 4210-4214.
[http://dx.doi.org/10.1016/j.bmcl.2008.05.068] [PMID: 18554905]
[91]
Oliveira, R.; Guedes, R.C.; Meireles, P.; Albuquerque, I.S.; Gonçalves, L.M.; Pires, E.; Bronze, M.R.; Gut, J.; Rosenthal, P.J.; Prudêncio, M.; Moreira, R.; O’Neill, P.M.; Lopes, F. Tetraoxane-pyrimidine nitrile hybrids as dual stage antimalarials. J. Med. Chem., 2014, 57(11), 4916-4923.
[http://dx.doi.org/10.1021/jm5004528] [PMID: 24824551]
[92]
Weldon, D.J.; Shah, F.; Chittiboyina, A.G.; Sheri, A.; Chada, R.R.; Gut, J.; Rosenthal, P.J.; Shivakumar, D.; Sherman, W.; Desai, P.; Jung, J.C.; Avery, M.A. Synthesis, biological evaluation, hydration site thermodynamics, and chemical reactivity analysis of α-keto substituted peptidomimetics for the inhibition of Plasmodium falciparum. Bioorg. Med. Chem. Lett., 2014, 24(5), 1274-1279.
[http://dx.doi.org/10.1016/j.bmcl.2014.01.062] [PMID: 24507921]
[93]
Musyoka, T.M.; Kanzi, A.M.; Lobb, K.A.; Tastan Bishop, Ö. Analysis of non-peptidic compounds as potential malarial inhibitors against Plasmodial cysteine proteases via integrated virtual screening workflow. J. Biomol. Struct. Dyn., 2016, 34(10), 2084-2101.
[http://dx.doi.org/10.1080/07391102.2015.1108231] [PMID: 26471975]
[94]
Bertoldo, J.B.; Chiaradia-Delatorre, L.D.; Mascarello, A.; Leal, P.C.; Cordeiro, M.N.S.; Nunes, R.J.; Sarduy, E.S.; Rosenthal, P.J.; Terenzi, H. Synthetic compounds from an in house library as inhibitors of falcipain-2 from Plasmodium falciparum. J. Enzyme Inhib. Med. Chem., 2015, 30(2), 299-307.
[http://dx.doi.org/10.3109/14756366.2014.920839] [PMID: 24964346]
[95]
Musyoka, T.M.; Kanzi, A.M.; Lobb, K.A.; Tastan Bishop, Ö. Structure based docking and molecular dynamic studies of plasmodial cysteine proteases against a South African natural compound and its analogs. Sci. Rep., 2016, 6(1), 23690.
[http://dx.doi.org/10.1038/srep23690] [PMID: 27030511]
[96]
Wang, L.; Zhang, S.; Zhu, J.; Zhu, L.; Liu, X.; Shan, L.; Huang, J.; Zhang, W.; Li, H. Identification of diverse natural products as falcipain-2 inhibitors through structure-based virtual screening. Bioorg. Med. Chem. Lett., 2014, 24(5), 1261-1264.
[http://dx.doi.org/10.1016/j.bmcl.2014.01.074] [PMID: 24530004]
[97]
Shah, F.; Mukherjee, P.; Gut, J.; Legac, J.; Rosenthal, P.J.; Tekwani, B.L.; Avery, M.A. Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library. J. Chem. Inf. Model., 2011, 51(4), 852-864.
[http://dx.doi.org/10.1021/ci200029y] [PMID: 21428453]
[98]
Hernández-González, J.E.; Salas-Sarduy, E.; Hernández Ramírez, L.F.; Pascual, M.J.; Álvarez, D.E.; Pabón, A.; Leite, V.B.P.; Pascutti, P.G.; Valiente, P.A. Identification of (4-(9H-fluoren-9-yl) piperazin-1-yl) methanone derivatives as falcipain 2 inhibitors active against Plasmodium falciparum cultures. Biochim. Biophys. Acta, Gen. Subj., 2018, 1862(12), 2911-2923.
[http://dx.doi.org/10.1016/j.bbagen.2018.09.015] [PMID: 30253205]
[99]
Zhu, J.; Chen, T.; Liu, J.; Ma, R.; Lu, W.; Huang, J.; Li, H.; Li, J.; Jiang, H. 2-(3,4-dihydro-4-oxothieno[2,3-d] pyrimidin-2-ylthio) acetamides as a new class of falcipain-2 inhibitors. 3. design, synthesis and biological evaluation. Molecules, 2009, 14(2), 785-797.
[http://dx.doi.org/10.3390/molecules14020785] [PMID: 19223827]
[100]
Liu, Y.; Cui, K.; Lu, W.; Luo, W.; Wang, J.; Huang, J.; Guo, C. Synthesis and antimalarial activity of novel dihydro-artemisinin derivatives. Molecules, 2011, 16(6), 4527-4538.
[http://dx.doi.org/10.3390/molecules16064527] [PMID: 21629181]
[101]
Liu, Y.; Lu, W.Q.; Cui, K.Q.; Luo, W.; Wang, J.; Guo, C. Synthesis and biological activities of novel artemisinin derivatives as cysteine protease falcipain-2 inhibitors. Arch. Pharm. Res., 2012, 35(9), 1525-1531.
[http://dx.doi.org/10.1007/s12272-012-0902-4] [PMID: 23054708]
[102]
Rana, D.; Kalamuddin, M.; Sundriyal, S.; Jaiswal, V.; Sharma, G.; Das Sarma, K.; Sijwali, P.S.; Mohmmed, A.; Malhotra, P.; Mahindroo, N. Identification of antimalarial leads with dual falcipain-2 and falcipain-3 inhibitory activity. Bioorg. Med. Chem., 2020, 28(1), 115155.
[http://dx.doi.org/10.1016/j.bmc.2019.115155] [PMID: 31744777]
[103]
Batra, S.; Sabnis, Y.A.; Rosenthal, P.J.; Avery, M.A. Structure-based approach to falcipain-2 inhibitors: Synthesis and biological evaluation of 1,6,7-trisubstituted dihydroisoquinolines and isoquinolines. Bioorg. Med. Chem., 2003, 11(10), 2293-2299.
[http://dx.doi.org/10.1016/S0968-0896(03)00117-2] [PMID: 12713840]
[104]
Sharma, K.; Shrivastava, A.; Mehra, R.N.; Deora, G.S.; Alam, M.M.; Zaman, M.S.; Akhter, M. Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium falciparum growth by dual target inhibition. Arch. Pharm., 2018, 351(1), 1700251.
[http://dx.doi.org/10.1002/ardp.201700251] [PMID: 29227011]
[105]
Singh, A.K.; Rajendran, V.; Pant, A.; Ghosh, P.C.; Singh, N.; Latha, N.; Garg, S.; Pandey, K.C.; Singh, B.K.; Rathi, B. Design, synthesis and biological evaluation of functionalized phthalimides: A new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite. Bioorg. Med. Chem., 2015, 23(8), 1817-1827.
[http://dx.doi.org/10.1016/j.bmc.2015.02.029] [PMID: 25766631]
[106]
Klayman, D.L.; Bartosevich, J.F.; Griffin, T.S.; Mason, C.J.; Scovill, J.P. 2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents. J. Med. Chem., 1979, 22(7), 855-862.
[http://dx.doi.org/10.1021/jm00193a020] [PMID: 376848]
[107]
Greenbaum, D.C.; Mackey, Z.; Hansell, E.; Doyle, P.; Gut, J.; Caffrey, C.R.; Lehrman, J.; Rosenthal, P.J.; McKerrow, J.H.; Chibale, K. Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi. J. Med. Chem., 2004, 47(12), 3212-3219.
[http://dx.doi.org/10.1021/jm030549j] [PMID: 15163200]
[108]
Chipeleme, A.; Gut, J.; Rosenthal, P.J.; Chibale, K. Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives against the cysteine protease falcipain-2 and a chloroquine resistant strain of Plasmodium falciparum. Bioorg. Med. Chem., 2007, 15(1), 273-282.
[http://dx.doi.org/10.1016/j.bmc.2006.09.055] [PMID: 17052908]
[109]
Chiyanzu, I.; Hansell, E.; Gut, J.; Rosenthal, P.J.; McKerrow, J.H.; Chibale, K. Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain. Bioorg. Med. Chem. Lett., 2003, 13(20), 3527-3530.
[http://dx.doi.org/10.1016/S0960-894X(03)00756-X] [PMID: 14505663]
[110]
Ehmke, V.; Heindl, C.; Rottmann, M.; Freymond, C.; Schweizer, W.B.; Brun, R.; Stich, A.; Schirmeister, T.; Diederich, F. Potent and selective inhibition of cysteine proteases from Plasmodium falciparum and Trypanosoma brucei. ChemMedChem, 2011, 6(2), 273-278.
[http://dx.doi.org/10.1002/cmdc.201000449] [PMID: 21275051]
[111]
Schirmeister, T.; Kaeppler, U. Non-peptidic inhibitors of cysteine proteases. Mini Rev. Med. Chem., 2003, 3(4), 361-373.
[http://dx.doi.org/10.2174/1389557033488079] [PMID: 12678829]
[112]
Liu, M.; Wilairat, P.; Go, M.L. Antimalarial alkoxylated and hydroxylated chalcones (corrected): Structure-activity relationship analysis. J. Med. Chem., 2001, 44(25), 4443-4452.
[http://dx.doi.org/10.1021/jm0101747] [PMID: 11728189]
[113]
Li, R.; Kenyon, G.L.; Cohen, F.E.; Chen, X.; Gong, B.; Dominguez, J.N.; Davidson, E.; Kurzban, G.; Miller, R.E.; Nuzum, E.O.; Rosenthal, P.J.; McKerrow, J.H. In vitro antimalarial activity of chalcones and their derivatives. J. Med. Chem., 1995, 38(26), 5031-5037.
[http://dx.doi.org/10.1021/jm00026a010] [PMID: 8544179]
[114]
Domínguez, J.N.; León, C.; Rodrigues, J.; Gamboa de Domínguez, N.; Gut, J.; Rosenthal, P.J. Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J. Med. Chem., 2005, 48(10), 3654-3658.
[http://dx.doi.org/10.1021/jm058208o] [PMID: 15887974]
[115]
Chen, M.; Theander, T.G.; Christensen, S.B.; Hviid, L.; Zhai, L.; Kharazmi, A.; Licochalcone, A. Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii infection. Antimicrob. Agents Chemother., 1994, 38(7), 1470-1475.
[http://dx.doi.org/10.1128/AAC.38.7.1470] [PMID: 7979274]
[116]
Chen, M.; Christensen, S.B.Ø.; Zhai, L.; Rasmussen, M.H.; Theander, T.G.; FrØkjaer, S.; Steffansen, B.; Davidsen, J.; Kharazmi, A. The novel oxygenated chalcone, 2,4-dimethoxy-4′-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparumin vitro and rodent parasites Plasmodium berghei and Plasmodium yoeliiin vivo. J. Infect. Dis., 1997, 176(5), 1327-1333.
[http://dx.doi.org/10.1086/514129] [PMID: 9359735]
[117]
Shah, F.; Wu, Y.; Gut, J.; Pedduri, Y.; Legac, J.; Rosenthal, P.J.; Avery, M.A. Design, synthesis and biological evaluation of novel benzothiazole and triazole analogs as falcipain inhibitors. MedChemComm, 2011, 2(12), 1201-1207.
[http://dx.doi.org/10.1039/c1md00129a]
[118]
Singh, A.; Kalamuddin, M.; Mohmmed, A.; Malhotra, P.; Hoda, N. Quinoline-triazole hybrids inhibit falcipain-2 and arrest the development of Plasmodium falciparum at the trophozoite stage. RSC Advances, 2019, 9(67), 39410-39421.
[http://dx.doi.org/10.1039/C9RA06571G] [PMID: 35540629]
[119]
Schmidt, I.; Pradel, G.; Sologub, L.; Golzmann, A.; Ngwa, C.J.; Kucharski, A.; Schirmeister, T.; Holzgrabe, U. Bistacrine derivatives as new potent antimalarials. Bioorg. Med. Chem., 2016, 24(16), 3636-3642.
[http://dx.doi.org/10.1016/j.bmc.2016.06.003] [PMID: 27316542]
[120]
Schmidt, I.; Göllner, S.; Fuß, A.; Stich, A.; Kucharski, A.; Schirmeister, T.; Katzowitsch, E.; Bruhn, H.; Miliu, A.; Krauth-Siegel, R.L.; Holzgrabe, U. Bistacrines as potential antitrypanosomal agents. Bioorg. Med. Chem., 2017, 25(16), 4526-4531.
[http://dx.doi.org/10.1016/j.bmc.2017.06.051] [PMID: 28698054]
[121]
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]
[122]
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]
[123]
Bhat, A.S.; Dustin Schaeffer, R.; Kinch, L.; Medvedev, K.E.; Grishin, N.V. Recent advances suggest increased influence of selective pressure in allostery. Curr. Opin. Struct. Biol., 2020, 62, 183-188.
[http://dx.doi.org/10.1016/j.sbi.2020.02.004] [PMID: 32302874]
[124]
Wagner, J.R.; Lee, C.T.; Durrant, J.D.; Malmstrom, R.D.; Feher, V.A.; Amaro, R.E. Emerging computational methods for the rational discovery of allosteric drugs. Chem. Rev., 2016, 116(11), 6370-6390.
[http://dx.doi.org/10.1021/acs.chemrev.5b00631] [PMID: 27074285]
[125]
Novinec, M.; Korenč, M.; Caflisch, A.; Ranganathan, R.; Lenarčič, B.; Baici, A. A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods. Nat. Commun., 2014, 5(1), 3287.
[http://dx.doi.org/10.1038/ncomms4287] [PMID: 24518821]
[126]
Novinec, M.; Lenarčič, B.; Baici, A. Probing the activity modification space of the cysteine peptidase cathepsin K with novel allosteric modifiers. PLoS One, 2014, 9(9), e106642.
[http://dx.doi.org/10.1371/journal.pone.0106642] [PMID: 25184245]
[127]
Novinec, M.; Rebernik, M.; Lenarčič, B. An allosteric site enables fine-tuning of cathepsin K by diverse effectors. FEBS Lett., 2016, 590(24), 4507-4518.
[http://dx.doi.org/10.1002/1873-3468.12495] [PMID: 27859061]
[128]
Marques, A.F.; Esser, D.; Rosenthal, P.J.; Kassack, M.U.; Lima, L.M.T.R. Falcipain-2 inhibition by suramin and suramin analogues. Bioorg. Med. Chem., 2013, 21(13), 3667-3673.
[http://dx.doi.org/10.1016/j.bmc.2013.04.047] [PMID: 23680445]
[129]
Marques, A.F.; Gomes, P.S.F.C.; Oliveira, P.L.; Rosenthal, P.J.; Pascutti, P.G.; Lima, L.M.T.R. Allosteric regulation of the Plasmodium falciparum cysteine protease falcipain-2 by heme. Arch. Biochem. Biophys., 2015, 573, 92-99.
[http://dx.doi.org/10.1016/j.abb.2015.03.007] [PMID: 25791019]
[130]
Okeke, C.J.; Musyoka, T.M.; Sheik Amamuddy, O.; Barozi, V.; Tastan Bishop, Ö. Allosteric pockets and dynamic residue network hubs of falcipain 2 in mutations including those linked to artemisinin resistance. Comput. Struct. Biotechnol. J., 2021, 19, 5647-5666.
[http://dx.doi.org/10.1016/j.csbj.2021.10.011] [PMID: 34745456]
[131]
Hernández González, J.E.; Hernández Alvarez, L.; Pascutti, P.G.; Leite, V.B.P. Prediction of noncompetitive inhibitor binding mode reveals promising site for allosteric modulation of falcipain-2. J. Phys. Chem. B, 2019, 123(34), 7327-7342.
[http://dx.doi.org/10.1021/acs.jpcb.9b05021] [PMID: 31366200]
[132]
Hernández González, J.E.; Salas-Sarduy, E.; Hernández Alvarez, L.; Barreto Gomes, D.E.; Pascutti, P.G.; Oostenbrink, C.; Leite, V.B.P. In silico identification of noncompetitive inhibitors targeting an uncharacterized allosteric site of falcipain-2. J. Comput. Aided Mol. Des., 2021, 35(10), 1067-1079.
[http://dx.doi.org/10.1007/s10822-021-00420-7] [PMID: 34617191]
[133]
Alberca, L.N.; Chuguransky, S.R.; Álvarez, C.L.; Talevi, A.; Salas-Sarduy, E. In silico guided drug repurposing: Discovery of new competitive and non-competitive inhibitors of falcipain-2. Front Chem., 2019, 7, 534.
[http://dx.doi.org/10.3389/fchem.2019.00534] [PMID: 31448257]
[134]
Hernández González, J.E.; Alberca, L.N.; Masforrol González, Y.; Reyes Acosta, O.; Talevi, A.; Salas-Sarduy, E. Tetracycline derivatives inhibit plasmodial cysteine protease falcipain-2 through binding to a distal allosteric site. J. Chem. Inf. Model., 2022, 62(1), 159-175.
[http://dx.doi.org/10.1021/acs.jcim.1c01189] [PMID: 34962803]
[135]
Pant, A.; Kumar, R.; Wani, N.A.; Verma, S.; Sharma, R.; Pande, V.; Saxena, A.K.; Dixit, R.; Rai, R.; Pandey, K.C. Allosteric site inhibitor disrupting auto-processing of malarial cysteine proteases. Sci. Rep., 2018, 8(1), 16193.
[http://dx.doi.org/10.1038/s41598-018-34564-8] [PMID: 30385827]
[136]
Stjernschantz, E.; Oostenbrink, C. Improved ligand-protein binding affinity predictions using multiple binding modes. Biophys. J., 2010, 98(11), 2682-2691.
[http://dx.doi.org/10.1016/j.bpj.2010.02.034] [PMID: 20513413]
[137]
Lindström, A.; Edvinsson, L.; Johansson, A.; Andersson, C.D.; Andersson, I.E.; Raubacher, F.; Linusson, A. Postprocessing of docked protein-ligand complexes using implicit solvation models. J. Chem. Inf. Model., 2011, 51(2), 267-282.
[http://dx.doi.org/10.1021/ci100354x] [PMID: 21309544]
[138]
Clark, A.J.; Tiwary, P.; Borrelli, K.; Feng, S.; Miller, E.B.; Abel, R.; Friesner, R.A.; Berne, B.J. Prediction of protein–ligand binding poses via a combination of induced fit docking and metadynamics simulations. J. Chem. Theory Comput., 2016, 12(6), 2990-2998.
[http://dx.doi.org/10.1021/acs.jctc.6b00201] [PMID: 27145262]
[139]
Desai, P.V.; Patny, A.; Sabnis, Y.; Tekwani, B.; Gut, J.; Rosenthal, P.; Srivastava, A.; Avery, M. Identification of novel parasitic cysteine protease inhibitors using virtual screening. 1. The ChemBridge database. J. Med. Chem., 2004, 47(26), 6609-6615.
[http://dx.doi.org/10.1021/jm0493717] [PMID: 15588096]
[140]
Sharma, R.K.; Younis, Y.; Mugumbate, G.; Njoroge, M.; Gut, J.; Rosenthal, P.J.; Chibale, K. Synthesis and structure–activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2. Eur. J. Med. Chem., 2015, 90, 507-518.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.061] [PMID: 25486422]
[141]
Desai, P.V.; Patny, A.; Gut, J.; Rosenthal, P.J.; Tekwani, B.; Srivastava, A.; Avery, M. Identification of novel parasitic cysteine protease inhibitors by use of virtual screening. 2. The available chemical directory. J. Med. Chem., 2006, 49(5), 1576-1584.
[http://dx.doi.org/10.1021/jm0505765] [PMID: 16509575]
[142]
Uddin, A.; Gupta, S.; Mohammad, T.; Shahi, D.; Hussain, A.; Alajmi, M.F.; El-Seedi, H.R.; Hassan, I.; Singh, S.; Abid, M. Target-based virtual screening of natural compounds identifies a potent antimalarial with selective falcipain-2 inhibitory activity. Front. Pharmacol., 2022, 13, 850176.
[http://dx.doi.org/10.3389/fphar.2022.850176] [PMID: 35462917]
[143]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[144]
Li, H.; Li, C.; Gui, C.; Luo, X.; Chen, K.; Shen, J.; Wang, X.; Jiang, H. GAsDock: A new approach for rapid flexible docking based on an improved multi-population genetic algorithm. Bioorganic Med. Chem., 2004, 14(18), 4671-4676.
[http://dx.doi.org/10.1016/j.bmcl.2004.06.091]
[145]
Wang, L.; Li, X.; Zhang, S.; Lu, W.; Liao, S.; Liu, X.; Shan, L.; Shen, X.; Jiang, H.; Zhang, W.; Huang, J.; Li, H. Natural products as a gold mine for selective matrix metalloproteinases inhibitors. Bioorg. Med. Chem., 2012, 20(13), 4164-4171.
[http://dx.doi.org/10.1016/j.bmc.2012.04.063] [PMID: 22658537]
[146]
Kubinyi, H. QSAR and 3D QSAR in drug design Part 1: methodology. Drug Discov. Today, 1997, 2(11), 457-467.
[http://dx.doi.org/10.1016/S1359-6446(97)01079-9]
[147]
Gálvez, J.; Gálvez-Llompart, M.; García-Domenech, R. Advances in Mathematical Chemistry and Applications; Basak, S.C.; Restrepo, G.; Villaveces, J.L., Eds.; Elsevier and Bentham Science Publisher, 2015, 1, pp. 161-195.
[148]
Chintakrindi, A.S.; Shaikh, M.S.; Coutinho, E.C. De novo design of 7-aminocoumarin derivatives as novel falcipain-3 inhibitors. J. Mol. Model., 2012, 18(4), 1481-1493.
[http://dx.doi.org/10.1007/s00894-011-1177-2] [PMID: 21785935]
[149]
Potshangbam, A.M.; Tanneeru, K.; Reddy, B.M.; Guruprasad, L. 3D-QSAR and molecular docking studies of 2-pyrimidinecarbonitrile derivatives as inhibitors against falcipain-3. Bioorg. Med. Chem. Lett., 2011, 21(23), 7219-7223.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.107] [PMID: 22018459]
[150]
Teixeira, C.; Gomes, J.R.B.; Couesnon, T.; Gomes, P. Molecular docking and 3D-quantitative structure activity relationship analyses of peptidyl vinyl sulfones: Plasmodium falciparum cysteine proteases inhibitors. J. Comput. Aided Mol. Des., 2011, 25(8), 763-775.
[http://dx.doi.org/10.1007/s10822-011-9459-4] [PMID: 21786172]
[151]
Wang, J.; Li, Y.; Yang, Y.; Zhang, S.; Yang, L. Profiling the structural determinants of heteroarylnitrile scaffold-based derivatives as falcipain-2 inhibitors by in silico methods. Curr. Med. Chem., 2013, 20(15), 2032-2042.
[http://dx.doi.org/10.2174/0929867311320150008] [PMID: 23410155]
[152]
Wang, J.; Li, F.; Li, Y.; Yang, Y.; Zhang, S.; Yang, L. Structural features of falcipain-3 inhibitors: An in silico study. Mol. Biosyst., 2013, 9(9), 2296-2310.
[http://dx.doi.org/10.1039/c3mb70105k] [PMID: 23765034]
[153]
Thillainayagam, M.; Anbarasu, A.; Ramaiah, S. Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum. J. Theor. Biol., 2016, 403, 110-128.
[http://dx.doi.org/10.1016/j.jtbi.2016.05.019] [PMID: 27185536]
[154]
Wolber, G.; Langer, T. LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J. Chem. Inf. Model., 2005, 45(1), 160-169.
[http://dx.doi.org/10.1021/ci049885e] [PMID: 15667141]
[155]
Seidel, T.; Bryant, S.D.; Ibis, G.; Poli, G.; Langer, T. 3D pharmacophore modeling techniques in computer-aided molecular design using LigandScout. J. Tutorials Chemoinform, 2017, 281, 279-309.
[http://dx.doi.org/10.1002/9781119161110.ch20]
[156]
Allangba, K.N.G.P.G.; Keita, M.; Kre N’Guessan, R.; Megnassan, E.; Frecer, V.; Miertus, S. Virtual design of novel Plasmodium falciparum cysteine protease falcipain-2 hybrid lactone–chalcone and isatin–chalcone inhibitors probing the S2 active site pocket. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 547-561.
[http://dx.doi.org/10.1080/14756366.2018.1564288] [PMID: 30696325]
[157]
Southall, N.T.; Dill, K.A.; Haymet, A.D.J. A view of the hydrophobic effect. J. Phys. Chem. B, 2002, 106(3), 521-533.
[http://dx.doi.org/10.1021/jp015514e]
[158]
Snyder, P.W.; Mecinović, J.; Moustakas, D.T.; Thomas, S.W., III; Harder, M.; Mack, E.T.; Lockett, M.R.; Héroux, A.; Sherman, W.; Whitesides, G.M. Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase. Proc. Natl. Acad. Sci. USA, 2011, 108(44), 17889-17894.
[http://dx.doi.org/10.1073/pnas.1114107108] [PMID: 22011572]
[159]
García-Sosa, A.T. Hydration properties of ligands and drugs in protein binding sites: Tightly-bound, bridging water molecules and their effects and consequences on molecular design strategies. J. Chem. Inf. Model., 2013, 53(6), 1388-1405.
[http://dx.doi.org/10.1021/ci3005786] [PMID: 23662606]
[160]
Young, T.; Abel, R.; Kim, B.; Berne, B.J.; Friesner, R.A. Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand binding. Proc. Natl. Acad. Sci. USA, 2007, 104(3), 808-813.
[http://dx.doi.org/10.1073/pnas.0610202104] [PMID: 17204562]
[161]
Abel, R.; Young, T.; Farid, R.; Berne, B.J.; Friesner, R.A. Role of the active-site solvent in the thermodynamics of factor Xa ligand binding. J. Am. Chem. Soc., 2008, 130(9), 2817-2831.
[http://dx.doi.org/10.1021/ja0771033] [PMID: 18266362]
[162]
Shah, F.; Gut, J.; Legac, J.; Shivakumar, D.; Sherman, W.; Rosenthal, P.J.; Avery, M.A. Computer-aided drug design of falcipain inhibitors: Virtual screening, structure-activity relationships, hydration site thermodynamics, and reactivity analysis. J. Chem. Inf. Model., 2012, 52(3), 696-710.
[http://dx.doi.org/10.1021/ci2005516] [PMID: 22332946]
[163]
Homeyer, N.; Gohlke, H. Free energy calculations by the molecular mechanics poisson−boltzmann surface area method. Mol. Inform., 2012, 31(2), 114-122.
[http://dx.doi.org/10.1002/minf.201100135] [PMID: 27476956]
[164]
Hernández González, J.E.; Hernández Alvarez, L.; Leite, V.B.P.; Pascutti, P.G. Water bridges play a key role in affinity and selectivity for malarial protease falcipain-2. J. Chem. Inf. Model., 2020, 60(11), 5499-5512.
[http://dx.doi.org/10.1021/acs.jcim.0c00294] [PMID: 32634311]
[165]
Pérez, B.C.; Teixeira, C.; Figueiras, M.; Gut, J.; Rosenthal, P.J.; Gomes, J.R.B.; Gomes, P. Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: Towards the development of potential dual action antimalarials. Eur. J. Med. Chem., 2012, 54, 887-899.
[http://dx.doi.org/10.1016/j.ejmech.2012.05.022] [PMID: 22683112]
[166]
Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Tunyasuvunakool, K.; Bates, R.; Žídek, A.; Potapenko, A.; Bridgland, A.; Meyer, C.; Kohl, S.A.A.; Ballard, A.J.; Cowie, A.; Romera-Paredes, B.; Nikolov, S.; Jain, R.; Adler, J.; Back, T.; Petersen, S.; Reiman, D.; Clancy, E.; Zielinski, M.; Steinegger, M.; Pacholska, M.; Berghammer, T.; Bodenstein, S.; Silver, D.; Vinyals, O.; Senior, A.W.; Kavukcuoglu, K.; Kohli, P.; Hassabis, D. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873), 583-589.
[http://dx.doi.org/10.1038/s41586-021-03819-2] [PMID: 34265844]
[167]
Gentile, F.; Yaacoub, J.C.; Gleave, J.; Fernandez, M.; Ton, A.T.; Ban, F.; Stern, A.; Cherkasov, A. Artificial intelligence–enabled virtual screening of ultra-large chemical libraries with deep docking. Nat. Protoc., 2022, 17(3), 672-697.
[http://dx.doi.org/10.1038/s41596-021-00659-2] [PMID: 35121854]
[168]
Mugumbate, G.; Newton, A.S.; Rosenthal, P.J.; Gut, J.; Moreira, R.; Chibale, K.; Guedes, R.C. Novel anti-Plasmodial hits identified by virtual screening of the ZINC database. J. Comput. Aided Mol. Des., 2013, 27(10), 859-871.
[http://dx.doi.org/10.1007/s10822-013-9685-z] [PMID: 24158745]
[169]
Bajorath, J. Deep machine learning for computer-aided drug design. Front. Drug Discov., 2022, 2, 829043.
[http://dx.doi.org/10.3389/fddsv.2022.829043]
[170]
Kumar, A.; Zhang, K.Y.J. Advances in the development of shape similarity methods and their application in drug discovery. Front Chem., 2018, 6, 315.
[http://dx.doi.org/10.3389/fchem.2018.00315] [PMID: 30090808]
[171]
Bhhatarai, B.; Walters, W.P.; Hop, C.E.C.A.; Lanza, G.; Ekins, S. Opportunities and challenges using artificial intelligence in ADME/Tox. Nat. Mater., 2019, 18(5), 418-422.
[http://dx.doi.org/10.1038/s41563-019-0332-5] [PMID: 31000801]

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