Login Register Cart 0
Review Article

寄生虫靶点的双重抑制：治疗疟疾和被忽视的热带病的宝贵策略

卷 29, 期 17, 2022

发表于: 10 August, 2021

页: [2952 - 2978] 页: 27

弟呕挨: 10.2174/0929867328666210810125309

价格: $65

摘要

尽管在过去几十年中做出了无数努力，但疟疾和被忽视的热带病仍然是发展中国家一个影响严重的健康问题。疟疾是最严重的寄生虫病之一，2019年有2亿多例病例和40万人死亡。由锥虫科引起的寄生虫病，即非洲人类锥虫病、恰加斯病和利什曼病，在所有被忽视的热带病中死亡率最高。在这种情况下，化疗仍然是第一个策略，旨在控制和消除这些疾病。然而，使用过时，不安全和效果不佳的药物，以及耐药性的开始，促使研究人员确定新的有效靶点。这一创新想法旨在开发多靶点配体，以解决在寄生虫生存中发挥关键作用的两个不同靶点，这可能是一种有价值的策略。由于这种方法，可以克服抗寄生虫药物的众所周知的局限性，例如毒性，快速耐药性和狭窄的作用范围。在这篇综述中，我们现在描述了文献中报道的具有抗寄生虫作用的最新多靶点配体，将注意力集中在它们与靶标的结合，抑制活性和潜在的治疗应用上。

关键词: 双重抑制，多靶点配体，疟疾，被忽视的热带病，非洲人类锥虫病，恰加斯病，利什曼病。

« Previous Next »
[1]
Uniting to Combact Neglected Tropical Diseases. 2021. Available from: https://unitingtocombatntds.org/ntds/ (Accessed on April 12 2021).
[2]
World Health Organization. Control of Neglected Tropical Diseases., Available from: https://www.who.int/teams/ control-of-neglected-tropical-diseases (Accessed on April 10 2021).
[3]
Bhattacharya, A.; Corbeil, A.; do Monte-Neto, R.L.; Fernandez-Prada, C. Of drugs and trypanosomatids: new tools and knowledge to reduce bottlenecks in drug discovery. Genes (Basel), 2020, 11(7), 722.
[http://dx.doi.org/10.3390/genes11070722] [PMID: 32610603]
[4]
World Health Organization. Malaria Available from: https://www.who.int/news-room/fact-sheets/detail/malaria (Accessed on April 10 2021).
[5]
Simon, G.G. Impacts of neglected tropical disease on incidence and progression of HIV/AIDS, tuberculosis, and malaria: scientific links. Int. J. Infect. Dis., 2016, 42, 54-57.
[http://dx.doi.org/10.1016/j.ijid.2015.11.006] [PMID: 26594012]
[6]
Espinoza-Fonseca, L.M. The benefits of the multi-target approach in drug design and discovery. Bioorg. Med. Chem., 2006, 14(4), 896-897.
[http://dx.doi.org/10.1016/j.bmc.2005.09.011] [PMID: 16203151]
[7]
Talevi, A. Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front. Pharmacol., 2015, 6, 205.
[http://dx.doi.org/10.3389/fphar.2015.00205] [PMID: 26441661]
[8]
Prati, F.; Uliassi, E.; Bolognesi, M.L. Two diseases, one approach: multitarget drug discovery in Alzheimer’s and neglected tropical diseases. MedChemComm, 2014, 5, 853-861.
[http://dx.doi.org/10.1039/C4MD00069B]
[9]
Ettari, R.; Previti, S.; Di Chio, C.; Zappalà, M. Zappala, M. Falcipain-2 and falcipain-3 inhibitors as promising antimalarial agents. Curr. Med. Chem., 2021, 28(15), 3010-3031.
[http://dx.doi.org/10.2174/0929867327666200730215316] [PMID: 32744954]
[10]
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]
[11]
Ettari, R.; Tamborini, L.; Angelo, I.C.; Micale, N.; Pinto, A.; De Micheli, C.; Conti, P. Inhibition of rhodesain as a novel therapeutic modality for human African trypanosomiasis. J. Med. Chem., 2013, 56(14), 5637-5658.
[http://dx.doi.org/10.1021/jm301424d] [PMID: 23611656]
[12]
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]
[13]
World Health Organization Geneva. 2020. Available from: https://www.who.int/teams/global-malaria-programme (Accessed on April 12 2021).
[14]
World Health Organization. 2021. Available from: https://www.who.int/teams/global-malaria-programme/guidelines-for-malaria (Accessed on April 11 2021).
[15]
Dondorp, A.M.; Fairhurst, R.M.; Slutsker, L.; Macarthur, J.R.; Breman, J.G.; Guerin, P.J.; Wellems, T.E.; Ringwald, P.; Newman, R.D.; Plowe, C.V. The threat of artemisinin-resistant malaria. N. Engl. J. Med., 2011, 365(12), 1073-1075.
[http://dx.doi.org/10.1056/NEJMp1108322] [PMID: 21992120]
[16]
Adepoju, P. RTS,S malaria vaccine pilots in three African countries. Lancet, 2019, 393(10182), 1685.
[http://dx.doi.org/10.1016/S0140-6736(19)30937-7] [PMID: 31034365]
[17]
Pholcharee, T.; Oyen, D.; Flores-Garcia, Y.; Gonzalez-Paez, G.; Han, Z.; Williams, K.L.; Volkmuth, W.; Emerling, D.; Locke, E.; Richter King, C.; Zavala, F.; Wilson, I.A. Structural and biophysical correlation of anti-NANP antibodies with in vivo protection against P. falciparum. Nat. Commun., 2021, 12(1), 1063.
[http://dx.doi.org/10.1038/s41467-021-21221-4] [PMID: 33594061]
[18]
Büscher, P.; Cecchi, G.; Jamonneau, V.; Priotto, G. Human African trypanosomiasis. Lancet, 2017, 390(10110), 2397-2409.
[http://dx.doi.org/10.1016/S0140-6736(17)31510-6] [PMID: 28673422]
[19]
Kennedy, P.G.E. Update on human African trypanosomiasis (sleeping sickness). J. Neurol., 2019, 266(9), 2334-2337.
[http://dx.doi.org/10.1007/s00415-019-09425-7] [PMID: 31209574]
[20]
DNDI Sleeping-sickness Available from: https://dndi.org/diseases/sleeping-sickness/ (Accessed on April 12 2021).
[21]
Delespaux, V.; de Koning, H.P. 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]
[22]
Lindner, A.K.; Lejon, V.; Chappuis, F.; Seixas, J.; Kazumba, L.; Barrett, M.P.; Mwamba, E.; Erphas, O.; Akl, E.A.; Villanueva, G.; Bergman, H.; Simarro, P.; Kadima Ebeja, A.; Priotto, G.; Franco, J.R. New WHO guidelines for treatment of gambiense human African trypanosomiasis including fexinidazole: substantial changes for clinical practice. Lancet Infect. Dis., 2020, 20(2), e38-e46.
[http://dx.doi.org/10.1016/S1473-3099(19)30612-7] [PMID: 31879061]
[23]
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]
[24]
Rassi, A., Jr; Rassi, A.; Marin-Neto, J.A. Chagas disease. Lancet, 2010, 375(9723), 1388-1402.
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[25]
DNDI Chagas disease. Available from: https://dndi.org/diseases/chagas/ (Accessed on April 12 2021).
[26]
Mansoldo, F.R.P.; Carta, F.; Angeli, A.; Cardoso, V.D.S.; Supuran, C.T.; Vermelho, A.B. Vermelho, A.B. Chagas disease: Perspectives on the past and present and challenges in drug discovery. Molecules, 2020, 25(22), 5483.
[http://dx.doi.org/10.3390/molecules25225483] [PMID: 33238613]
[27]
Torres-Guerrero, E.; Quintanilla-Cedillo, M.R.; Ruiz-Esmenjaud, J.; Arenas, R. Leishmaniasis: a review. F1000 Res., 2017, 6, 750.
[http://dx.doi.org/10.12688/f1000research.11120.1] [PMID: 28649370]
[28]
DNDi Visceral-leishmaniasis. Available from: https://dndi.org/diseases/visceral-leishmaniasis/ (Accessed on April 12 2021).
[29]
Singh, N.; Kumar, M.; Singh, R.K. Leishmaniasis: current status of available drugs and new potential drug targets. Asian Pac. J. Trop. Med., 2012, 5(6), 485-497.
[http://dx.doi.org/10.1016/S1995-7645(12)60084-4] [PMID: 22575984]
[30]
de Menezes, J.P.; Guedes, C.E.; Petersen, A.L.; Fraga, D.B.; Veras, P.S. Advances in development of new treatment for leishmaniasis. BioMed Res. Int., 2015, 2015, 815023.
[http://dx.doi.org/10.1155/2015/815023] [PMID: 26078965]
[31]
Bolognesi, M.L. Polypharmacology in a single drug: multitarget drugs. Curr. Med. Chem., 2013, 20(13), 1639-1645.
[http://dx.doi.org/10.2174/0929867311320130004] [PMID: 23410164]
[32]
Morphy, R.; Rankovic, Z. Fragments, network biology and designing multiple ligands. Drug Discov. Today, 2007, 12(3-4), 156-160.
[http://dx.doi.org/10.1016/j.drudis.2006.12.006] [PMID: 17275736]
[33]
Francis, S.E.; Sullivan, D.J., Jr; Goldberg, D.E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol., 1997, 51, 97-123.
[http://dx.doi.org/10.1146/annurev.micro.51.1.97] [PMID: 9343345]
[34]
Qidwai, T. Hemoglobin degrading proteases of Plasmodium falciparum as antimalarial drug targets. Curr. Drug Targets, 2015, 16(10), 1133-1141.
[http://dx.doi.org/10.2174/1389450116666150304104123] [PMID: 25738296]
[35]
Le Bonniec, S.; Deregnaucourt, C.; Redeker, V.; Banerjee, R.; Grellier, P.; Goldberg, D.E.; Schrével, J. Plasmepsin II, an acidic hemoglobinase from the Plasmodium falciparum food vacuole, is active at neutral pH on the host erythrocyte membrane skeleton. J. Biol. Chem., 1999, 274(20), 14218-14223.
[http://dx.doi.org/10.1074/jbc.274.20.14218] [PMID: 10318841]
[36]
Dhawan, S.; Dua, M.; Chishti, A.H.; Hanspal, M. Ankyrin peptide blocks falcipain-2-mediated malaria parasite release from red blood cells. J. Biol. Chem., 2003, 278(32), 30180-30186.
[http://dx.doi.org/10.1074/jbc.M305132200] [PMID: 12775709]
[37]
Tasdemir, D.; Lack, G.; Brun, R.; Rüedi, P.; Scapozza, L.; Perozzo, R. Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J. Med. Chem., 2006, 49(11), 3345-3353.
[http://dx.doi.org/10.1021/jm0600545] [PMID: 16722653]
[38]
Jin, H.; Xu, Z.; Cui, K.; Zhang, T.; Lu, W.; Huang, J. Dietary flavonoids fisetin and myricetin: dual inhibitors of Plasmodium falciparum falcipain-2 and plasmepsin II. Fitoterapia, 2014, 94, 55-61.
[http://dx.doi.org/10.1016/j.fitote.2014.01.017] [PMID: 24468190]
[39]
Dahl, E.L.; Rosenthal, P.J. Biosynthesis, localization, and processing of falcipain cysteine proteases of Plasmodium falciparum. Mol. Biochem. Parasitol., 2005, 139(2), 205-212.
[http://dx.doi.org/10.1016/j.molbiopara.2004.11.009] [PMID: 15664655]
[40]
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]
[41]
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]
[42]
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. USA, 2006, 103(31), 11503-11508.
[http://dx.doi.org/10.1073/pnas.0600489103] [PMID: 16864794]
[43]
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]
[44]
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]
[45]
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]
[46]
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]
[47]
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]
[48]
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]
[49]
Pereira, P.H.S.; Curra, C.; Garcia, C.R.S. Ubiquitin proteasome system as a potential drug target for malaria. Curr. Top. Med. Chem., 2018, 18(5), 315-320.
[http://dx.doi.org/10.2174/1568026618666180427145308] [PMID: 29701143]
[50]
Mata-Cantero, L.; Chaparro, M.J.; Colmenarejo, G.; Cid, C.; Cortes Cabrera, A.; Rodriguez, M.S.; Martín, J.; Gamo, F.J.; Gomez-Lorenzo, M.G. Gomez-Lorenzo, M. G. Identification of small molecules disrupting the ubiquitin proteasome system in malaria. ACS Infect. Dis., 2019, 5(12), 2105-2117.
[http://dx.doi.org/10.1021/acsinfecdis.9b00216] [PMID: 31644867]
[51]
Aminake, M.N.; Arndt, H.D.; Pradel, G. The proteasome of malaria parasites: A multi-stage drug target for chemotherapeutic intervention? Int. J. Parasitol. Drugs Drug Resist., 2012, 2, 1-10.
[http://dx.doi.org/10.1016/j.ijpddr.2011.12.001] [PMID: 24533266]
[52]
Prasad, R. Atul; Kolla, V.K.; Legac, J.; Singhal, N.; Navale, R.; Rosenthal, P.J.; Sijwali, P.S. Blocking Plasmodium falciparum development via dual inhibition of hemoglobin degradation and the ubiquitin proteasome system by MG132. PLoS One, 2013, 8(9), e73530.
[http://dx.doi.org/10.1371/journal.pone.0073530] [PMID: 24023882]
[53]
Raimondi, M.V.; Randazzo, O.; La Franca, M.; Barone, G.; Vignoni, E.; Rossi, D.; Collina, S. Collina, S. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules, 2019, 24(6), 1140.
[http://dx.doi.org/10.3390/molecules24061140] [PMID: 30909399]
[54]
DeJarnette, C.; Luna-Tapia, A.; Estredge, L.R.; Palmer, G.E. Dihydrofolate reductase is a valid target for antifungal development in the human pathogen Candida albicans. MSphere, 2020, 5(3), e00374-e00320.
[http://dx.doi.org/10.1128/mSphere.00374-20] [PMID: 32581079]
[55]
Gangjee, A.; Kurup, S.; Namjoshi, O. Dihydrofolate reductase as a target for chemotherapy in parasites. Curr. Pharm. Des., 2007, 13(6), 609-639.
[http://dx.doi.org/10.2174/138161207780162827] [PMID: 17346178]
[56]
Hawser, S.; Lociuro, S.; Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol., 2006, 71(7), 941-948.
[http://dx.doi.org/10.1016/j.bcp.2005.10.052] [PMID: 16359642]
[57]
Chen, M.J.; Shimada, T.; Moulton, A.D.; Cline, A.; Humphries, R.K.; Maizel, J.; Nienhuis, A.W. The functional human dihydrofolate reductase gene. J. Biol. Chem., 1984, 259(6), 3933-3943.
[http://dx.doi.org/10.1016/S0021-9258(17)43186-3] [PMID: 6323448]
[58]
Blakley, R.L. Eukaryotic dihydrofolate reductase. Adv. Enzymol. Relat. Areas Mol. Biol., 1995, 70, 23-102.
[PMID: 8638484]
[59]
Cao, H.; Gao, M.; Zhou, H.; Skolnick, J. The crystal structure of a tetrahydrofolate-bound dihydrofolate reductase reveals the origin of slow product release. Commun. Biol., 2018, 1(226)
[http://dx.doi.org/10.1038/s42003-018-0236-y]
[60]
Locasale, J.W. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer, 2013, 13(8), 572-583.
[http://dx.doi.org/10.1038/nrc3557] [PMID: 23822983]
[61]
McBreairty, L.E.; Bertolo, R.F. The dynamics of methionine supply and demand during early development. Appl. Physiol. Nutr. Metab., 2016, 41(6), 581-587.
[http://dx.doi.org/10.1139/apnm-2015-0577] [PMID: 27177124]
[62]
Bustos, D.G.; Canfield, C.J.; Canete-Miguel, E.; Hutchinson, D.B. Atovaquone-proguanil compared with chloroquine and chloroquine-sulfadoxine-pyrimethamine for treatment of acute Plasmodium falciparum malaria in the Philippines. J. Infect. Dis., 1999, 179(6), 1587-1590.
[http://dx.doi.org/10.1086/314770] [PMID: 10228090]
[63]
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]
[64]
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]
[65]
Nzila, A.; Rottmann, M.; Chitnumsub, P.; Kiara, S.M.; Kamchonwongpaisan, S.; Maneeruttanarungroj, C.; Taweechai, S.; Yeung, B.K.; Goh, A.; Lakshminarayana, S.B.; Zou, B.; Wong, J.; Ma, N.L.; Weaver, M.; Keller, T.H.; Dartois, V.; Wittlin, S.; Brun, R.; Yuthavong, Y.; Diagana, T.T. Preclinical evaluation of the antifolate QN254, 5-chloro- N′6′-(2,5-dimethoxy-benzyl)-quinazoline-2,4,6-triamine, as an antimalarial drug candidate. Antimicrob. Agents Chemother., 2010, 54(6), 2603-2610.
[http://dx.doi.org/10.1128/AAC.01526-09] [PMID: 20350951]
[66]
Rastelli, G.; Sirawaraporn, W.; Sompornpisut, P.; Vilaivan, T.; Kamchonwongpaisan, S.; Quarrell, R.; Lowe, G.; Thebtaranonth, Y.; Yuthavong, Y. Interaction of pyrimethamine, cycloguanil, WR99210 and their analogues with Plasmodium falciparum dihydrofolate reductase: Structural basis of antifolate resistance. Bioorg. Med. Chem., 2000, 8(5), 1117-1128.
[http://dx.doi.org/10.1016/S0968-0896(00)00022-5] [PMID: 10882022]
[67]
Chen, W.; Yao, X.; Huang, Z.; Mao, F.; Guan, L.; Tang, Y.; Jiang, H.; Li, J.; Huang, J.; Jiang, L.; Zhu, J. Novel dual inhibitors against FP-2 and PfDHFR as potential antimalarial agents: design, synthesis and biological evaluation. Chin. Chem. Lett., 2019, 30(1), 250-254.
[http://dx.doi.org/10.1016/j.cclet.2017.11.041]
[68]
McGowan, S. Working in concert: The metalloaminopeptidases from Plasmodium falciparum. Curr. Opin. Struct. Biol., 2013, 23(6), 828-835.
[http://dx.doi.org/10.1016/j.sbi.2013.07.015] [PMID: 23948130]
[69]
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]
[70]
Stack, C.M.; Lowther, J.; Cunningham, E.; Donnelly, S.; Gardiner, D.L.; Trenholme, K.R.; Skinner-Adams, T.S.; Teuscher, F.; Grembecka, J.; Mucha, A.; Kafarski, P.; Lua, L.; Bell, A.; Dalton, J.P. Characterization of the Plasmodium falciparum M17 leucyl aminopeptidase. A protease involved in amino acid regulation with potential for antimalarial drug development. J. Biol. Chem., 2007, 282(3), 2069-2080.
[http://dx.doi.org/10.1074/jbc.M609251200] [PMID: 17107951]
[71]
McGowan, S.; Porter, C.J.; Lowther, J.; Stack, C.M.; Golding, S.J.; Skinner-Adams, T.S.; Trenholme, K.R.; Teuscher, F.; Donnelly, S.M.; Grembecka, J.; Mucha, A.; Kafarski, P.; Degori, R.; Buckle, A.M.; Gardiner, D.L.; Whisstock, J.C.; Dalton, J.P. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc. Natl. Acad. Sci. USA, 2009, 106(8), 2537-2542.
[http://dx.doi.org/10.1073/pnas.0807398106] [PMID: 19196988]
[72]
McGowan, S.; Oellig, C.A.; Birru, W.A.; Caradoc-Davies, T.T.; Stack, C.M.; Lowther, J.; Skinner-Adams, T.; Mucha, A.; Kafarski, P.; Grembecka, J.; Trenholme, K.R.; Buckle, A.M.; Gardiner, D.L.; Dalton, J.P.; Whisstock, J.C. Structure of the Plasmodium falciparum M17 aminopeptidase and significance for the design of drugs targeting the neutral exopeptidases. Proc. Natl. Acad. Sci. USA, 2010, 107(6), 2449-2454.
[http://dx.doi.org/10.1073/pnas.0911813107] [PMID: 20133789]
[73]
Kannan Sivaraman, K.; Paiardini, A.; Sieńczyk, M.; Ruggeri, C.; Oellig, C.A.; Dalton, J.P.; Scammells, P.J.; Drag, M.; McGowan, S. Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum. J. Med. Chem., 2013, 56(12), 5213-5217.
[http://dx.doi.org/10.1021/jm4005972] [PMID: 23713488]
[74]
Mistry, S.N.; Drinkwater, N.; Ruggeri, C.; Sivaraman, K.K.; Loganathan, S.; Fletcher, S.; Drag, M.; Paiardini, A.; Avery, V.M.; Scammells, P.J.; McGowan, S. Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors. J. Med. Chem., 2014, 57(21), 9168-9183.
[http://dx.doi.org/10.1021/jm501323a] [PMID: 25299353]
[75]
Ruggeri, C.; Drinkwater, N.; Sivaraman, K.K.; Bamert, R.S.; McGowan, S.; Paiardini, A. Identification and validation of a potent dual inhibitor of the P. falciparum M1 and M17 aminopeptidases using virtual screening. PLoS One, 2015, 10(9), e0138957.
[http://dx.doi.org/10.1371/journal.pone.0138957] [PMID: 26406322]
[76]
Drinkwater, N.; Vinh, N.B.; Mistry, S.N.; Bamert, R.S.; Ruggeri, C.; Holleran, J.P.; Loganathan, S.; Paiardini, A.; Charman, S.A.; Powell, A.K.; Avery, V.M.; McGowan, S.; Scammells, P.J. Potent dual inhibitors of Plasmodium falciparum M1 and M17 aminopeptidases through optimization of S1 pocket interactions. Eur. J. Med. Chem., 2016, 110, 43-64.
[http://dx.doi.org/10.1016/j.ejmech.2016.01.015] [PMID: 26807544]
[77]
Nasamu, A.S.; Glushakova, S.; Russo, I.; Vaupel, B.; Oksman, A.; Kim, A.S.; Fremont, D.H.; Tolia, N.; Beck, J.R.; Meyers, M.J.; Niles, J.C.; Zimmerberg, J.; Goldberg, D.E. Plasmepsins IX and X are essential and druggable mediators of malaria parasite egress and invasion. Science, 2017, 358(6362), 518-522.
[http://dx.doi.org/10.1126/science.aan1478] [PMID: 29074774]
[78]
Alaganan, A.; Singh, P.; Chitnis, C.E. Molecular mechanisms that mediate invasion and egress of malaria parasites from red blood cells. Curr. Opin. Hematol., 2017, 24(3), 208-214.
[http://dx.doi.org/10.1097/MOH.0000000000000334] [PMID: 28306665]
[79]
Favuzza, P.; de Lera Ruiz, M.; Thompson, J.K.; Triglia, T.; Ngo, A.; Steel, R.W.J.; Vavrek, M.; Christensen, J.; Healer, J.; Boyce, C.; Guo, Z.; Hu, M.; Khan, T.; Murgolo, N.; Zhao, L.; Penington, J.S.; Reaksudsan, K.; Jarman, K.; Dietrich, M.H.; Richardson, L.; Guo, K.Y.; Lopaticki, S.; Tham, W.H.; Rottmann, M.; Papenfuss, T.; Robbins, J.A.; Boddey, J.A.; Sleebs, B.E.; Sabroux, H.J.; McCauley, J.A.; Olsen, D.B.; Cowman, A.F. Cowman, A.F. Dual plasmepsin-targeting antimalarial agents disrupt multiple stages of the malaria parasite life cycle. Cell Host Microbe, 2020, 27(4), 642-658.e12.
[http://dx.doi.org/10.1016/j.chom.2020.02.005] [PMID: 32109369]
[80]
Ciana, C.L.; Siegrist, R.; Aissaoui, H.; Marx, L.; Racine, S.; Meyer, S.; Binkert, C.; de Kanter, R.; Fischli, C.; Wittlin, S.; Boss, C. Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold. Bioorg. Med. Chem. Lett., 2013, 23(3), 658-662.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.118] [PMID: 23260352]
[81]
Pino, P.; Caldelari, R.; Mukherjee, B.; Vahokoski, J.; Klages, N.; Maco, B.; Collins, C.R.; Blackman, M.J.; Kursula, I.; Heussler, V.; Brochet, M.; Soldati-Favre, D. A multistage antimalarial targets the plasmepsins IX and X essential for invasion and egress. Science, 2017, 358(6362), 522-528.
[http://dx.doi.org/10.1126/science.aaf8675] [PMID: 29074775]
[82]
Munsamy, G.; Agoni, C.; Soliman, M.E.S. A dual target of Plasmepsin IX and X: Unveiling the atomistic superiority of a core chemical scaffold in malaria therapy. J. Cell. Biochem., 2018, 120(5), 7876-7887.
[http://dx.doi.org/10.1002/jcb.28062] [PMID: 30430636]
[83]
Green, J.L.; Moon, R.W.; Whalley, D.; Bowyer, P.W.; Wallace, C.; Rochani, A.; Nageshan, R.K.; Howell, S.A.; Grainger, M.; Jones, H.M.; Ansell, K.H.; Chapman, T.M.; Taylor, D.L.; Osborne, S.A.; Baker, D.A.; Tatu, U.; Holder, A.A. Imidazopyridazine inhibitors of Plasmodium falciparum calcium-dependent protein kinase 1 also target cyclic GMP-dependent protein kinase and heat shock protein 90 to kill the parasite at different stages of intracellular development. Antimicrob. Agents Chemother., 2015, 60(3), 1464-1475.
[http://dx.doi.org/10.1128/AAC.01748-15] [PMID: 26711771]
[84]
McNamara, C.W.; Lee, M.C.; Lim, C.S.; Lim, S.H.; Roland, J.; Simon, O.; Yeung, B.K.; Chatterjee, A.K.; McCormack, S.L.; Manary, M.J.; Zeeman, A.M.; Dechering, K.J.; Kumar, T.S.; Henrich, P.P.; Gagaring, K.; Ibanez, M.; Kato, N.; Kuhen, K.L.; Fischli, C.; Nagle, A.; Rottmann, M.; Plouffe, D.M.; Bursulaya, B.; Meister, S.; Rameh, L.; Trappe, J.; Haasen, D.; Timmerman, M.; Sauerwein, R.W.; Suwanarusk, R.; Russell, B.; Renia, L.; Nosten, F.; Tully, D.C.; Kocken, C.H.; Glynne, R.J.; Bodenreider, C.; Fidock, D.A.; Diagana, T.T.; Winzeler, E.A. Targeting Plasmodium PI(4)K to eliminate malaria. Nature, 2013, 504(7479), 248-253.
[http://dx.doi.org/10.1038/nature12782] [PMID: 24284631]
[85]
Rotella, D.; Siekierka, J.; Bhanot, P. Bhanot, P. Plasmodium falciparum cGMP-dependent protein kinase - a novel chemotherapeutic target. Front. Microbiol., 2021, 11, 610408.
[http://dx.doi.org/10.3389/fmicb.2020.610408] [PMID: 33613463]
[86]
Cheuka, P.M.; Centani, L.; Arendse, L.B.; Fienberg, S.; Wambua, L.; Renga, S.S.; Dziwornu, G.A.; Kumar, M.; Lawrence, N.; Taylor, D.; Wittlin, S.; Coertzen, D.; Reader, J.; van der Watt, M.; Birkholtz, L.M.; Chibale, K. New amidated 3,6-diphenylated imidazopyridazines with potent antiplasmodium activity are dual inhibitors of Plasmodium phosphatidylinositol-4-kinase and cGMP-dependent protein kinase. ACS Infect. Dis., 2021, 7(1), 34-46.
[http://dx.doi.org/10.1021/acsinfecdis.0c00481] [PMID: 33319990]
[87]
Stickles, A.M.; Ting, L.M.; Morrisey, J.M.; Li, Y.; Mather, M.W.; Meermeier, E.; Pershing, A.M.; Forquer, I.P.; Miley, G.P.; Pou, S.; Winter, R.W.; Hinrichs, D.J.; Kelly, J.X.; Kim, K.; Vaidya, A.B.; Riscoe, M.K.; Nilsen, A. Inhibition of cytochrome bc1 as a strategy for single-dose, multi-stage antimalarial therapy. Am. J. Trop. Med. Hyg., 2015, 92(6), 1195-1201.
[http://dx.doi.org/10.4269/ajtmh.14-0553] [PMID: 25918204]
[88]
Phillips, M.A.; Rathod, P.K. Plasmodium dihydroorotate dehydrogenase: A promising target for novel anti-malarial chemotherapy. Infect. Disord. Drug Targets, 2010, 10(3), 226-239.
[http://dx.doi.org/10.2174/187152610791163336] [PMID: 20334617]
[89]
Dickerman, B.K.; Elsworth, B.; Cobbold, S.A.; Nie, C.Q.; McConville, M.J.; Crabb, B.S.; Gilson, P.R. Identification of inhibitors that dually target the new permeability pathway and dihydroorotate dehydrogenase in the blood stage of Plasmodium falciparum. Sci. Rep., 2016, 6, 37502.
[http://dx.doi.org/10.1038/srep37502] [PMID: 27874068]
[90]
Rawat, R.; Verma, S.M. An exclusive computational insight toward molecular mechanism of MMV007571, a multitarget inhibitor of Plasmodium falciparum. J. Biomol. Struct. Dyn., 2020, 38(18), 5362-5373.
[http://dx.doi.org/10.1080/07391102.2019.1700165] [PMID: 31790334]
[91]
Rawat, R.; Verma, S.M. High-throughput virtual screening approach involving pharmacophore mapping, ADME filtering, molecular docking and MM-GBSA to identify new dual target inhibitors of PfDHODH and PfCytbc1 complex to combat drug resistant malaria. J. Biomol. Struct. Dyn., 2020, 1-12.
[http://dx.doi.org/10.1080/07391102.2020.1784288] [PMID: 32579074]
[92]
Mackey, Z.B.; O’Brien, T.C.; Greenbaum, D.C.; Blank, R.B.; McKerrow, J.H. A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei. J. Biol. Chem., 2004, 279(46), 48426-48433.
[http://dx.doi.org/10.1074/jbc.M402470200] [PMID: 15326171]
[93]
Mallari, J.P.; Shelat, A.; Kosinski, A.; Caffrey, C.R.; Connelly, M.; Zhu, F.; McKerrow, J.H.; Guy, R.K. Discovery of trypanocidal thiosemicarbazone inhibitors of rhodesain and TbcatB. Bioorg. Med. Chem. Lett., 2008, 18(9), 2883-2885.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.083] [PMID: 18420405]
[94]
Mallari, J.P.; Shelat, A.A.; Kosinski, A.; Caffrey, C.R.; Connelly, M.; Zhu, F.; McKerrow, J.H.; Guy, R.K. Structure-guided development of selective TbcatB inhibitors. J. Med. Chem., 2009, 52(20), 6489-6493.
[http://dx.doi.org/10.1021/jm900908p] [PMID: 19769357]
[95]
Mallari, J.P.; Shelat, A.A.; Obrien, T.; Caffrey, C.R.; Kosinski, A.; Connelly, M.; Harbut, M.; Greenbaum, D.; McKerrow, J.H.; Guy, R.K. Development of potent purine-derived nitrile inhibitors of the trypanosomal protease TbcatB. J. Med. Chem., 2008, 51(3), 545-552.
[http://dx.doi.org/10.1021/jm070760l] [PMID: 18173229]
[96]
Inglese, J.; Auld, D.S.; Jadhav, A.; Johnson, R.L.; Simeonov, A.; Yasgar, A.; Zheng, W.; Austin, C.P. Quantitative high-throughput screening: A titration-based approach that efficiently identifies biological activities in large chemical libraries. Proc. Natl. Acad. Sci. USA, 2006, 103(31), 11473-11478.
[http://dx.doi.org/10.1073/pnas.0604348103] [PMID: 16864780]
[97]
Mott, B.T.; Ferreira, R.S.; Simeonov, A.; Jadhav, A.; Ang, K.K.; Leister, W.; Shen, M.; Silveira, J.T.; Doyle, P.S.; Arkin, M.R.; McKerrow, J.H.; Inglese, J.; Austin, C.P.; Thomas, C.J.; Shoichet, B.K.; Maloney, D.J. Identification and optimization of inhibitors of Trypanosomal cysteine proteases: cruzain, rhodesain, and TbCatB. J. Med. Chem., 2010, 53(1), 52-60.
[http://dx.doi.org/10.1021/jm901069a] [PMID: 19908842]
[98]
Menzies, S.K.; Tulloch, L.B.; Florence, G.J.; Smith, T.K. The trypanosome alternative oxidase: a potential drug target? Parasitology, 2018, 145(2), 175-183.
[http://dx.doi.org/10.1017/S0031182016002109] [PMID: 27894362]
[99]
Balogun, E.O.; Inaoka, D.K.; Shiba, T.; Kido, Y.; Nara, T.; Aoki, T.; Honma, T.; Tanaka, A.; Inoue, M.; Matsuoka, S.; Michels, P.A.; Harada, S.; Kita, K. Biochemical characterization of highly active Trypanosoma brucei gambiense glycerol kinase, a promising drug target. J. Biochem., 2013, 154(1), 77-84.
[http://dx.doi.org/10.1093/jb/mvt037] [PMID: 23620597]
[100]
Nakamura, K.; Fujioka, S.; Fukumoto, S.; Inoue, N.; Sakamoto, K.; Hirata, H.; Kido, Y.; Yabu, Y.; Suzuki, T.; Watanabe, Y.; Saimoto, H.; Akiyama, H.; Kita, K. Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies. Parasitol. Int., 2010, 59(4), 560-564.
[http://dx.doi.org/10.1016/j.parint.2010.07.006] [PMID: 20688188]
[101]
Chaudhuri, M.; Ott, R.D.; Hill, G.C. Trypanosome alternative oxidase: from molecule to function. Trends Parasitol., 2006, 22(10), 484-491.
[http://dx.doi.org/10.1016/j.pt.2006.08.007] [PMID: 16920028]
[102]
Ohashi-Suzuki, M.; Yabu, Y.; Ohshima, S.; Nakamura, K.; Kido, Y.; Sakamoto, K.; Kita, K.; Ohta, N.; Suzuki, T. Differential kinetic activities of glycerol kinase among African trypanosome species: phylogenetic and therapeutic implications. J. Vet. Med. Sci., 2011, 73(5), 615-621.
[http://dx.doi.org/10.1292/jvms.10-0481] [PMID: 21187682]
[103]
Balogun, E.O.; Inaoka, D.K.; Shiba, T.; Tsuge, C.; May, B.; Sato, T.; Kido, Y.; Nara, T.; Aoki, T.; Honma, T.; Tanaka, A.; Inoue, M.; Matsuoka, S.; Michels, P.A.M.; Watanabe, Y.I.; Moore, A.L.; Harada, S.; Kita, K. Discovery of trypanocidal coumarins with dual inhibition of both the glycerol kinase and alternative oxidase of Trypanosoma brucei brucei. FASEB J., 2019, 33(11), 13002-13013.
[http://dx.doi.org/10.1096/fj.201901342R] [PMID: 31525300]
[104]
Ebiloma, G.U.; Katsoulis, E.; Igoli, J.O.; Gray, A.I.; De Koning, H.P. Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes. Sci. Rep., 2018, 8(1), 4613.
[http://dx.doi.org/10.1038/s41598-018-22908-3] [PMID: 29545637]
[105]
Ebiloma, G.U.; Igoli, J.O.; Katsoulis, E.; Donachie, A.M.; Eze, A.; Gray, A.I.; de Koning, H.P. Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals. J. Ethnopharmacol., 2017, 202, 256-264.
[http://dx.doi.org/10.1016/j.jep.2017.03.028] [PMID: 28336470]
[106]
Verlinde, C.L.; Hannaert, V.; Blonski, C.; Willson, M.; Périé, J.J.; Fothergill-Gilmore, L.A.; Opperdoes, F.R.; Gelb, M.H.; Hol, W.G.; Michels, P.A. Glycolysis as a target for the design of new anti-trypanosome drugs. Drug Resist. Updat., 2001, 4(1), 50-65.
[http://dx.doi.org/10.1054/drup.2000.0177] [PMID: 11512153]
[107]
Coley, A.F.; Dodson, H.C.; Morris, M.T.; Morris, J.C. Glycolysis in the african trypanosome: Targeting enzymes and their subcellular compartments for therapeutic development. Mol. Biol. Int., 2011, 2011, 123702.
[http://dx.doi.org/10.4061/2011/123702] [PMID: 22091393]
[108]
Krauth-Siegel, L.R.; Comini, M.A.; Schlecker, T. The trypanothione system. Subcell. Biochem., 2007, 44, 231-251.
[http://dx.doi.org/10.1007/978-1-4020-6051-9_11] [PMID: 18084897]
[109]
Turrens, J.F. Oxidative stress and antioxidant defenses: A target for the treatment of diseases caused by parasitic protozoa. Mol. Aspects Med., 2004, 25(1-2), 211-220.
[http://dx.doi.org/10.1016/j.mam.2004.02.021] [PMID: 15051329]
[110]
Bolognesi, M.L.; Lizzi, F.; Perozzo, R.; Brun, R.; Cavalli, A. Synthesis of a small library of 2-phenoxy-1,4-naphthoquinone and 2-phenoxy-1,4-anthraquinone derivatives bearing anti-trypanosomal and anti-leishmanial activity. Bioorg. Med. Chem. Lett., 2008, 18(7), 2272-2276.
[http://dx.doi.org/10.1016/j.bmcl.2008.03.009] [PMID: 18353643]
[111]
Pieretti, S.; Haanstra, J.R.; Mazet, M.; Perozzo, R.; Bergamini, C.; Prati, F.; Fato, R.; Lenaz, G.; Capranico, G.; Brun, R.; Bakker, B.M.; Michels, P.A.; Scapozza, L.; Bolognesi, M.L.; Cavalli, A. Naphthoquinone derivatives exert their antitrypanosomal activity via a multi-target mechanism. PLoS Negl. Trop. Dis., 2013, 7(1), e2012.
[http://dx.doi.org/10.1371/journal.pntd.0002012] [PMID: 23350008]
[112]
Lizzi, F.; Veronesi, G.; Belluti, F.; Bergamini, C.; López-Sánchez, A.; Kaiser, M.; Brun, R.; Krauth-Siegel, R.L.; Hall, D.G.; Rivas, L.; Bolognesi, M.L. Conjugation of quinones with natural polyamines: toward an expanded antitrypanosomatid profile. J. Med. Chem., 2012, 55(23), 10490-10500.
[http://dx.doi.org/10.1021/jm301112z] [PMID: 23153330]
[113]
Muronetz, V.I.; Melnikova, A.K.; Barinova, K.V.; Schmalhausen, E.V. Schmalhausen, E.V. Inhibitors of glyceraldehyde 3-phosphate dehydrogenase and unexpected effects of its reduced activity. Biochemistry (Mosc.), 2019, 84(11), 1268-1279.
[http://dx.doi.org/10.1134/S0006297919110051] [PMID: 31760917]
[114]
Battista, T.; Colotti, G.; Ilari, A.; Fiorillo, A. Targeting trypanothione reductase, a key enzyme in the redox trypanosomatid metabolism, to develop new drugs against leishmaniasis and trypanosomiases. Molecules, 2020, 25(8), 1924.
[http://dx.doi.org/10.3390/molecules25081924] [PMID: 32326257]
[115]
Belluti, F.; Uliassi, E.; Veronesi, G.; Bergamini, C.; Kaiser, M.; Brun, R.; Viola, A.; Fato, R.; Michels, P.A.; Krauth-Siegel, R.L.; Cavalli, A.; Bolognesi, M.L. Toward the development of dual-targeted glyceraldehyde-3-phosphate dehydrogenase/trypanothione reductase inhibitors against Trypanosoma brucei and Trypanosoma cruzi. ChemMedChem, 2014, 9(2), 371-382.
[http://dx.doi.org/10.1002/cmdc.201300399] [PMID: 24403089]
[116]
Pavão, F.; Castilho, M.S.; Pupo, M.T.; Dias, R.L.; Correa, A.G.; Fernandes, J.B.; da Silva, M.F.; Mafezoli, J.; Vieira, P.C.; Oliva, G. Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution. FEBS Lett., 2002, 520(1-3), 13-17.
[http://dx.doi.org/10.1016/S0014-5793(02)02700-X] [PMID: 12044862]
[117]
Barrett, M.P.; Gilbert, I.H. Targeting of toxic compounds to the trypanosome’s interior. Adv. Parasitol., 2006, 63, 125-183.
[http://dx.doi.org/10.1016/S0065-308X(06)63002-9] [PMID: 17134653]
[118]
Zuccotto, F.; Martin, A.C.; Laskowski, R.A.; Thornton, J.M.; Gilbert, I.H. Dihydrofolate reductase: a potential drug target in trypanosomes and leishmania. J. Comput. Aided Mol. Des., 1998, 12(3), 241-257.
[http://dx.doi.org/10.1023/A:1016085005275] [PMID: 9749368]
[119]
Bello, A.R.; Nare, B.; Freedman, D.; Hardy, L.; Beverley, S.M. PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc. Natl. Acad. Sci. USA, 1994, 91(24), 11442-11446.
[http://dx.doi.org/10.1073/pnas.91.24.11442] [PMID: 7972081]
[120]
Kimuda, M.P.; Laming, D.; Hoppe, H.C.; Tastan Bishop, Ö. Identification of novel potential inhibitors of pteridine reductase 1 in Trypanosoma brucei via computational structure-based approaches and in vitro inhibition assays. Molecules, 2019, 24(1), 142.
[http://dx.doi.org/10.3390/molecules24010142] [PMID: 30609681]
[121]
Anderson, A.C. Targeting DHFR in parasitic protozoa. Drug Discov. Today, 2005, 10(2), 121-128.
[http://dx.doi.org/10.1016/S1359-6446(04)03308-2] [PMID: 15718161]
[122]
Michels, P.A.; Bringaud, F.; Herman, M.; Hannaert, V. Metabolic functions of glycosomes in trypanosomatids. Biochim. Biophys. Acta, 2006, 1763(12), 1463-1477.
[http://dx.doi.org/10.1016/j.bbamcr.2006.08.019] [PMID: 17023066]
[123]
Chambers, J.W.; Fowler, M.L.; Morris, M.T.; Morris, J.C. The anti-trypanosomal agent lonidamine inhibits Trypanosoma brucei hexokinase 1. Mol. Biochem. Parasitol., 2008, 158(2), 202-207.
[http://dx.doi.org/10.1016/j.molbiopara.2007.12.013] [PMID: 18262292]
[124]
D’Antonio, E.L.; Deinema, M.S.; Kearns, S.P.; Frey, T.A.; Tanghe, S.; Perry, K.; Roy, T.A.; Gracz, H.S.; Rodriguez, A.; D’Antonio, J. Structure-based approach to the identification of a novel group of selective glucosamine analogue inhibitors of Trypanosoma cruzi glucokinase. Mol. Biochem. Parasitol., 2015, 204(2), 64-76.
[http://dx.doi.org/10.1016/j.molbiopara.2015.12.004] [PMID: 26778112]
[125]
Mercaldi, G.F.; D’Antonio, E.L.; Aguessi, A.; Rodriguez, A.; Cordeiro, A.T. Discovery of antichagasic inhibitors by high-throughput screening with Trypanosoma cruzi glucokinase. Bioorg. Med. Chem. Lett., 2019, 29(15), 1948-1953.
[http://dx.doi.org/10.1016/j.bmcl.2019.05.037] [PMID: 31133533]
[126]
Omolabi, K.F.; Odeniran, P.O.; Olotu, F.A.; Soliman, M.E.S. A mechanistic probe into the dual inhibition of T. cruzi glucokinase and hexokinase in chagas disease treatment - a stone killing two birds? Chem. Biodivers., 2021, 18(2), e2000863.
[http://dx.doi.org/10.1002/cbdv.202000863] [PMID: 33411971]
[127]
Cortés-Figueroa, A.A.; Pérez-Torres, A.; Salaiza, N.; Cabrera, N.; Escalona-Montaño, A.; Rondán, A.; Aguirre-García, M.; Gómez-Puyou, A.; Pérez-Montfort, R.; Becker, I. A monoclonal antibody that inhibits Trypanosoma cruzi growth in vitro and its reaction with intracellular triosephosphate isomerase. Parasitol. Res., 2008, 102(4), 635-643.
[http://dx.doi.org/10.1007/s00436-007-0803-5] [PMID: 18046577]
[128]
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]
[129]
Cazzulo, J.J.; Stoka, V.; Turk, V. Cruzipain, the major cysteine proteinase from the protozoan parasite Trypanosoma cruzi. Biol. Chem., 1997, 378(1), 1-10.
[PMID: 9049059]
[130]
Fleisch, H.; Russell, R.G.; Francis, M.D. Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science, 1969, 165(3899), 1262-1264.
[http://dx.doi.org/10.1126/science.165.3899.1262] [PMID: 5803538]
[131]
Francis, M.D.; Russell, R.G.; Fleisch, H. Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science, 1969, 165(3899), 1264-1266.
[http://dx.doi.org/10.1126/science.165.3899.1264] [PMID: 4308521]
[132]
Martin, M.B.; Grimley, J.S.; Lewis, J.C.; Heath, H.T., III; Bailey, B.N.; Kendrick, H.; Yardley, V.; Caldera, A.; Lira, R.; Urbina, J.A.; Moreno, S.N.; Docampo, R.; Croft, S.L.; Oldfield, E. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum: A potential route to chemotherapy. J. Med. Chem., 2001, 44(6), 909-916.
[http://dx.doi.org/10.1021/jm0002578] [PMID: 11300872]
[133]
Hosfield, D.J.; Zhang, Y.; Dougan, D.R.; Broun, A.; Tari, L.W.; Swanson, R.V.; Finn, J. Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis. J. Biol. Chem., 2004, 279(10), 8526-8529.
[http://dx.doi.org/10.1074/jbc.C300511200] [PMID: 14672944]
[134]
Cheng, F.; Oldfield, E. Inhibition of isoprene biosynthesis pathway enzymes by phosphonates, bisphosphonates, and diphosphates. J. Med. Chem., 2004, 47(21), 5149-5158.
[http://dx.doi.org/10.1021/jm040036s] [PMID: 15456258]
[135]
Szajnman, S.H.; Ravaschino, E.L.; Docampo, R.; Rodriguez, J.B. Synthesis and biological evaluation of 1-amino-1,1-bisphosphonates derived from fatty acids against Trypanosoma cruzi targeting farnesyl pyrophosphate synthase. Bioorg. Med. Chem. Lett., 2005, 15(21), 4685-4690.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.060] [PMID: 16143525]
[136]
Szajnman, S.H.; Montalvetti, A.; Wang, Y.; Docampo, R.; Rodriguez, J.B. Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase. Bioorg. Med. Chem. Lett., 2003, 13(19), 3231-3235.
[http://dx.doi.org/10.1016/S0960-894X(03)00663-2] [PMID: 12951099]
[137]
Szajnman, S.H.; García Liñares, G.E.; Li, Z.H.; Jiang, C.; Galizzi, M.; Bontempi, E.J.; Ferella, M.; Moreno, S.N.; Docampo, R.; Rodriguez, J.B. Synthesis and biological evaluation of 2-alkylaminoethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii targeting farnesyl diphosphate synthase. Bioorg. Med. Chem., 2008, 16(6), 3283-3290.
[http://dx.doi.org/10.1016/j.bmc.2007.12.010] [PMID: 18096393]
[138]
Magnin, D.R.; Biller, S.A.; Dickson, J.K., Jr; Logan, J.V.; Lawrence, R.M.; Chen, Y.; Sulsky, R.B.; Ciosek, C.P., Jr; Harrity, T.W.; Jolibois, K.G. 1,1-Bisphosphonate squalene synthase inhibitors: Interplay between the isoprenoid subunit and the diphosphate surrogate. J. Med. Chem., 1995, 38(14), 2596-2605.
[http://dx.doi.org/10.1021/jm00014a012] [PMID: 7629799]
[139]
Rodrígues-Poveda, C.A.; González-Pacanowska, D.; Szajnman, S.H.; Rodríguez, J.B. 2-alkylaminoethyl-1,1-bisphosphonic acids are potent inhibitors of the enzymatic activity of Trypanosoma cruzi squalene synthase. Antimicrob. Agents Chemother., 2012, 56(8), 4483-4486.
[http://dx.doi.org/10.1128/AAC.00796-12] [PMID: 22585217]
[140]
Urbina, J.A. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop., 2010, 115(1-2), 55-68.
[http://dx.doi.org/10.1016/j.actatropica.2009.10.023] [PMID: 19900395]
[141]
Ivanetich, K.M.; Santi, D.V. Thymidylate synthase-dihydrofolate reductase in protozoa. Exp. Parasitol., 1990, 70(3), 367-371.
[http://dx.doi.org/10.1016/0014-4894(90)90119-W] [PMID: 2178951]
[142]
Nare, B.; Luba, J.; Hardy, L.W.; Beverley, S. New approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity. Parasitology, 1997, 114(Suppl.), S101-S110.
[http://dx.doi.org/10.1017/S0031182097001133] [PMID: 9309772]
[143]
Teixeira, B.V.F.; Teles, A.L.B.; Silva, S.G.D.; Brito, C.C.B.; Freitas, H.F.; Pires, A.B.L.; Froes, T.Q.; Castilho, M.S. Dual and selective inhibitors of pteridine reductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Leishmania chagasi. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1439-1450.
[http://dx.doi.org/10.1080/14756366.2019.1651311] [PMID: 31409157]
[144]
Teles, A.L.B.; Silva, R.R.; Ko, M.; Ferreira, G.M.; Pita, S.D.R.; Trossini, G.H.G.; Carvalho, P.; Castilho, M.S. Identification, characterization and molecular modelling studies of Schistosoma mansoni dihydrofolate reductase inhibitors: From assay development to hit identification. Curr. Top. Med. Chem., 2018, 18(5), 406-417.
[http://dx.doi.org/10.2174/1568026618666180509150134] [PMID: 29741139]

Rights & Permissions Print Cite
Article Metrics
20
1
© 2024 Bentham Science Publishers | Privacy Policy