Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Ruthenium Metallotherapeutics: Novel Approaches to Combatting Parasitic Infections

Author(s): Nicole S. Britten and Jonathan A. Butler*

Volume 29, Issue 31, 2022

Published on: 10 June, 2022

Page: [5159 - 5178] Pages: 20

DOI: 10.2174/0929867329666220401105444

Price: $65

Abstract

Human parasitic infections cause a combined global mortality rate of over one million people per annum and represent some of the most challenging diseases for medical intervention. Current chemotherapeutic strategies often require prolonged treatment, coupled with subsequent drug-induced cytotoxic morbidity to the host, while resistance generation is also a major concern. Metals have been used extensively throughout the history of medicine, with more recent applications as anticancer and antimicrobial agents. Ruthenium metallotherapeutic antiparasitic agents are highly effective at targeting a range of key parasites, including the causative agents of malaria, trypanosomiasis, leishmaniasis, amoebiasis, toxoplasmosis and other orphan diseases, while demonstrating lower cytotoxicity profiles than current treatment strategies. Generally, such compounds also demonstrate activity against multiple cellular target sites within parasites, including inhibition of enzyme function, cell membrane perturbation, and alterations to metabolic pathways, therefore reducing the opportunity for resistance generation. This review provides a comprehensive and subjective analysis of the rapidly developing area of ruthenium metal- based antiparasitic chemotherapeutics, in the context of rational drug design and potential clinical approaches to combatting human parasitic infections.

Keywords: Antiparasitic, ruthenium, malaria, trypanosomiasis, leishmaniasis, amoebiasis, metallotherapeutic, parasitic infections.

« Previous Next »
[1]
Hayes, A.M.; Morris, D.J.; Clarkson, G.J.; Wills, M. A class of ruthenium(II) catalyst for asymmetric transfer hydrogenations of ketones. J. Am. Chem. Soc., 2005, 127(20), 7318-7319.
[http://dx.doi.org/10.1021/ja051486s] [PMID: 15898773]
[2]
Luft, J.H. Ruthenium red and violet. I. Chemistry, purification, methods of use for electron microscopy and mechanism of action. Anat. Rec., 1971, 171(3), 347-368.
[http://dx.doi.org/10.1002/ar.1091710302] [PMID: 4108333]
[3]
Shulman, A.; Dwyer, F.P. Metal chelates in biological systems. Chelat. Agents Metal Chelat., 1964, 1, 383-439.
[4]
Allardyce, C.S.; Dyson, P.J. Ruthenium in medicine: Current clinical uses and future prospects. Platin. Met. Rev., 2001, 45, 62.
[5]
Dwyer, F.P.; Reid, I.K.; Shulman, A.; Laycock, G.M.; Dixson, S. The biological actions of 1,10-phenanthroline and 2,2′-bipyridine hydrochlorides, quaternary salts and metal chelates and related compounds. 1. Bacteriostatic action on selected gram-positive, gram-negative and acid-fast bacteria. Aust. J. Exp. Biol. Med. Sci., 1969, 47(2), 203-218.
[http://dx.doi.org/10.1038/icb.1969.21] [PMID: 4307583]
[6]
Metcalfe, C.; Thomas, J.A. Kinetically inert transition metal complexes that reversibly bind to DNA. Chem. Soc. Rev., 2003, 32(4), 215-224.
[http://dx.doi.org/10.1039/b201945k] [PMID: 12875027]
[7]
Li, F.; Collins, J.G.; Keene, F.R. Ruthenium complexes as antimicrobial agents. Chem. Soc. Rev., 2015, 44(8), 2529-2542.
[http://dx.doi.org/10.1039/C4CS00343H] [PMID: 25724019]
[8]
Southam, H.M.; Butler, J.A.; Chapman, J.A.; Poole, R.K. The microbiology of ruthenium complexes. Adv. Microb. Physiol., 2017, 71(71), 1-96.
[PMID: 28760320]
[9]
Martínez, A.; Rajapakse, C.S.; Naoulou, B.; Kopkalli, Y.; Davenport, L.; Sánchez-Delgado, R.A. The mechanism of antimalarial action of the ruthenium(II)-chloroquine complex [RuCl(2)(CQ)] (2). J. Biol. Inorg. Chem., 2008, 13(5), 703-712.
[http://dx.doi.org/10.1007/s00775-008-0356-9] [PMID: 18305967]
[10]
Corrêa, R.S.; da Silva, M.M.; Graminha, A.E.; Meira, C.S.; Santos, J.A.; Moreira, D.R.; Soares, M.B.; Von Poelhsitz, G.; Castellano, E.E.; Bloch, C., Jr; Cominetti, M.R.; Batista, A.A. Ruthenium(II) complexes of 1,3-thiazolidine-2-thione: Cytotoxicity against tumor cells and anti-Trypanosoma cruzi activity enhanced upon combination with benznidazole. J. Inorg. Biochem., 2016, 156(156), 153-163.
[http://dx.doi.org/10.1016/j.jinorgbio.2015.12.024] [PMID: 26795676]
[11]
Barbosa, M.I.; Corrêa, R.S.; de Oliveira, K.M.; Rodrigues, C.; Ellena, J.; Nascimento, O.R.; Rocha, V.P.; Nonato, F.R.; Macedo, T.S.; Barbosa-Filho, J.M.; Soares, M.B.; Batista, A.A. Antiparasitic activities of novel ruthenium/lapachol complexes. J. Inorg. Biochem., 2014, 136(136), 33-39.
[http://dx.doi.org/10.1016/j.jinorgbio.2014.03.009] [PMID: 24727183]
[12]
Jackson, Y.; Wyssa, B.; Chappuis, F. Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas’ disease. J. Antimicrob. Chemother., 2020, 75(3), 690-696.
[http://dx.doi.org/10.1093/jac/dkz473] [PMID: 31754690]
[13]
Agarwal, A.; Kanekar, S.; Sabat, S.; Thamburaj, K. Metronidazole-induced cerebellar toxicity. Neurol. Int., 2016, 8(1), 6365.
[http://dx.doi.org/10.4081/ni.2016.6365] [PMID: 27127600]
[14]
Fairlamb, A.H.; Horn, D. Melarsoprol resistance in African trypanosomiasis. Trends Parasitol., 2018, 34(6), 481-492.
[http://dx.doi.org/10.1016/j.pt.2018.04.002] [PMID: 29705579]
[15]
Talapko, J.; Škrlec, I.; Alebić, T.; Jukić, M.; Včev, A. Malaria: The past and the present. Microorganisms, 2019, 7(6), 179.
[http://dx.doi.org/10.3390/microorganisms7060179] [PMID: 31234443]
[16]
WHO. World malaria report 2019. 2019. Available from: https://www.who.int/malaria/publications/world-malaria-report-2019/en/
[17]
Rei Yan, S.L.; Wakasuqui, F.; Wrenger, C. Point-of-care tests for malaria: Speeding up the diagnostics at the bedside and challenges in malaria cases detection. Diagn. Microbiol. Infect. Dis., 2020, 98(3), 115122.
[http://dx.doi.org/10.1016/j.diagmicrobio.2020.115122] [PMID: 32711185]
[18]
Stringer, T.; Quintero, M.A.S.; Wiesner, L.; Smith, G.S.; Nordlander, E. Evaluation of PTA-derived ruthenium(II) and iridium(III) quinoline complexes against chloroquine-sensitive and resistant strains of the Plasmodium falciparum malaria parasite. J. Inorg. Biochem., 2019, 191, 164-173.
[http://dx.doi.org/10.1016/j.jinorgbio.2018.11.018] [PMID: 30529881]
[19]
Adams, M.; de Kock, C.; Smith, P.J.; Land, K.M.; Liu, N.; Hopper, M.; Hsiao, A.; Burgoyne, A.R.; Stringer, T.; Meyer, M.; Wiesner, L.; Chibale, K.; Smith, G.S. Improved antiparasitic activity by incorporation of organosilane entities into half-sandwich ruthenium(II) and rhodium(III) thiosemicarbazone complexes. Dalton Trans., 2015, 44(5), 2456-2468.
[http://dx.doi.org/10.1039/C4DT03234A] [PMID: 25559246]
[20]
Coppée, R.; Sabbagh, A.; Clain, J. Structural and evolutionary analyses of the Plasmodium falciparum chloroquine resistance transporter. Sci. Rep., 2020, 10(1), 4842.
[http://dx.doi.org/10.1038/s41598-020-61181-1] [PMID: 32179795]
[21]
Rylands, L.I.; Welsh, A.; Maepa, K.; Stringer, T.; Taylor, D.; Chibale, K.; Smith, G.S. Structure-activity relationship studies of antiplasmodial cyclometallated ruthenium(II), rhodium(III) and iridium(III) complexes of 2-phenylbenzimidazoles. Eur. J. Med. Chem., 2019, 161, 11-21.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.019] [PMID: 30342422]
[22]
Cutillas, N.; Yellol, G.S.; de Haro, C.; Vicente, C.; Rodríguez, V.; Ruiz, J. Anticancer cyclometalated complexes of platinum group metals and gold. Coord. Chem. Rev., 2013, 257(19-20), 2784-2797.
[http://dx.doi.org/10.1016/j.ccr.2013.03.024]
[23]
Thangavel, P.; Viswanath, B.; Kim, S. Recent developments in the nanostructured materials functionalized with ruthenium complexes for targeted drug delivery to tumors. Int. J. Nanomed., 2017, 12, 2749-2758.
[http://dx.doi.org/10.2147/IJN.S131304] [PMID: 28435255]
[24]
Souza, N.B.; Aguiar, A.C.; Oliveira, A.C.; Top, S.; Pigeon, P.; Jaouen, G.; Goulart, M.O.; Krettli, A.U. Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites. Mem. Inst. Oswaldo Cruz, 2015, 110(8), 981-988.
[http://dx.doi.org/10.1590/0074-02760150163] [PMID: 26602875]
[25]
Ekengard, E.; Glans, L.; Cassells, I.; Fogeron, T.; Govender, P.; Stringer, T.; Chellan, P.; Lisensky, G.C.; Hersh, W.H.; Doverbratt, I.; Lidin, S.; de Kock, C.; Smith, P.J.; Smith, G.S.; Nordlander, E. Antimalarial activity of ruthenium(II) and osmium(II) arene complexes with mono- and bidentate chloroquine analogue ligands. Dalton Trans., 2015, 44(44), 19314-19329.
[http://dx.doi.org/10.1039/C5DT02410B] [PMID: 26491831]
[26]
Sánchez-Delgado, R.A.; Navarro, M.; Pérez, H.; Urbina, J.A. Toward a novel metal-based chemotherapy against tropical diseases. 2. Synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes. J. Med. Chem., 1996, 39(5), 1095-1099.
[http://dx.doi.org/10.1021/jm950729w] [PMID: 8676344]
[27]
Chellan, P.; Land, K.M.; Shokar, A.; Au, A.; An, S.H.; Taylor, D.; Smith, P.J.; Riedel, T.; Dyson, P.J.; Chibale, K.; Smith, G.S. Synthesis and evaluation of new polynuclear organometallic Ru(II), Rh(III) and Ir(III) pyridyl ester complexes as in vitro antiparasitic and antitumor agents. Dalton Trans., 2014, 43(2), 513-526.
[http://dx.doi.org/10.1039/C3DT52090K] [PMID: 24121555]
[28]
Franz, A.K.; Wilson, S.O. Organosilicon molecules with medicinal applications. J. Med. Chem., 2013, 56(2), 388-405.
[http://dx.doi.org/10.1021/jm3010114] [PMID: 23061607]
[29]
Blunder, M.; Hurkes, N.; Spirk, S.; List, M.; Pietschnig, R. Silanetriols as in vitro inhibitors for AChE. Bioorg. Med. Chem. Lett., 2011, 21(1), 363-365.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.139] [PMID: 21111617]
[30]
Martínez, A.; Carreon, T.; Iniguez, E.; Anzellotti, A.; Sánchez, A.; Tyan, M.; Sattler, A.; Herrera, L.; Maldonado, R.A.; Sánchez-Delgado, R.A. Searching for new chemotherapies for tropical diseases: Ruthenium-clotrimazole complexes display high in vitro activity against Leishmania major and Trypanosoma cruzi and low toxicity toward normal mammalian cells. J. Med. Chem., 2012, 55(8), 3867-3877.
[http://dx.doi.org/10.1021/jm300070h] [PMID: 22448965]
[31]
Hillard, E.A.; Pigeon, P.; Vessières, A.; Amatore, C.; Jaouen, G. The influence of phenolic hydroxy substitution on the electron transfer and anti-cancer properties of compounds based on the 2-ferrocenyl-1-phenyl-but-1-ene motif. Dalton Trans., 2007, 43(43), 5073-5081.
[http://dx.doi.org/10.1039/b705030e] [PMID: 17992292]
[32]
WHO. Chagas disease (also known as American trypanosomiasis). 2020. Available from: https://www.who.int/news- room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis).
[33]
Radisic, M.V.; Repetto, S.A. American trypanosomiasis (Chagas disease) in solid organ transplantation. Transpl. Infect. Dis., 2020, 22(6), e13429.
[http://dx.doi.org/10.1111/tid.13429] [PMID: 32738158]
[34]
Sesti-Costa, R.; Carneiro, Z.A.; Silva, M.C.; Santos, M.; Silva, G.K.; Milanezi, C.; da Silva, R.S.; Silva, J.S. Ruthenium complex with benznidazole and nitric oxide as a new candidate for the treatment of chagas disease. PLoS Negl.Trop. Dis., 2014, 8(10), e3207.
[http://dx.doi.org/10.1371/journal.pntd.0003207]
[35]
Fandzloch, M.; Arriaga, J.M.M.; Sánchez-Moreno, M.; Wojtczak, A.; Jezierska, J.; Sitkowski, J.; Wiśniewska, J.; Salas, J.M.; Łakomska, I. Strategies for overcoming tropical disease by ruthenium complexes with purine analog: Application against Leishmania spp. and Trypanosoma cruzi. J. Inorg. Biochem., 2017, 176(176), 144-155.
[http://dx.doi.org/10.1016/j.jinorgbio.2017.08.018] [PMID: 28910663]
[36]
Ong, YC; Roy, S; Andrews, PC; Gasser, G Metal compounds against neglected tropical diseases. Chem. Rev., 2018, 119(2), 730-796.
[37]
Sarniguet, C.; Toloza, J.; Cipriani, M.; Lapier, M.; Vieites, M.; Toledano-Magaña, Y.; García-Ramos, J.C.; Ruiz-Azuara, L.; Moreno, V.; Maya, J.D.; Azar, C.O.; Gambino, D.; Otero, L. Water-soluble ruthenium complexes bearing activity against protozoan parasites. Biol. Trace Elem. Res., 2014, 159(1-3), 379-392.
[http://dx.doi.org/10.1007/s12011-014-9964-0] [PMID: 24740394]
[38]
Romero, A.H.; López, S.E. In silico molecular docking studies of new potential 4-phthalazinyl-hydrazones on selected Trypanosoma cruzi and Leishmania enzyme targets. J. Mol. Graph. Model., 2017, 76, 313-329.
[http://dx.doi.org/10.1016/j.jmgm.2017.07.013] [PMID: 28763686]
[39]
Magalhaes Moreira, D.R.; de Oliveira, A.D.; Teixeira de Moraes Gomes, P.A.; de Simone, C.A.; Villela, F.S.; Ferreira, R.S.; da Silva, A.C.; dos Santos, T.A.; Brelaz de Castro, M.C.; Pereira, V.R.; Leite, A.C. Conformational restriction of aryl thiosemicarbazones produces potent and selective anti-Trypanosoma cruzi compounds which induce apoptotic parasite death. Eur. J. Med. Chem., 2014, 75, 467-478.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.001] [PMID: 24561675]
[40]
Das, P.; Alam, M.N.; Paik, D.; Karmakar, K.; De, T.; Chakraborti, T. Protease inhibitors in potential drug development for Leishmaniasis. Indian J. Biochem. Biophys., 2013, 50(5), 363-376.
[PMID: 24772958]
[41]
Moreira, D.R.; Leite, A.C.; dos Santos, R.R.; Soares, M.B. Approaches for the development of new anti-Trypanosoma cruzi agents. Curr. Drug Targets, 2009, 10(3), 212-231.
[http://dx.doi.org/10.2174/138945009787581140] [PMID: 19275558]
[42]
Bastos, T.M.; Barbosa, M.I.; da Silva, M.M.; da C Júnior, J.W.; Meira, C.S.; Guimaraes, E.T.; Ellena, J.; Moreira, D.R.; Batista, A.A.; Soares, M.B. Nitro/nitrosyl-ruthenium complexes are potent and selective anti-Trypanosoma cruzi agents causing autophagy and necrotic parasite death. Antimicrob. Agents Chemother., 2014, 58(10), 6044-6055.
[http://dx.doi.org/10.1128/AAC.02765-14] [PMID: 25092707]
[43]
Donnici, C.L.; Araújo, M.H.; Oliveira, H.S.; Moreira, D.R.; Pereira, V.R.; de Assis Souza, M.; de Castro, M.C.; Leite, A.C. Ruthenium complexes endowed with potent anti-Trypanosoma cruzi activity: Synthesis, biological characterization and structure-activity relationships. Bioorg. Med. Chem., 2009, 17(14), 5038-5043.
[http://dx.doi.org/10.1016/j.bmc.2009.05.071] [PMID: 19539479]
[44]
Sánchez-Delgado, R.A.; Navarro, M.; Lazardi, K.; Atencio, R.; Capparelli, M.; Vargas, F.; Urbina, J.A.; Bouillez, A.; Noels, A.F.; Masi, D. Toward a novel metal based chemotherapy against tropical diseases 4. Synthesis and characterization of new metal-clotrimazole complexes and evaluation of their activity against Trypanosoma cruzi. Inorg. Chim. Acta, 1998, 275, 528-540.
[http://dx.doi.org/10.1016/S0020-1693(98)00114-5]
[45]
Iniguez, E.; Sánchez, A.; Vasquez, M.A.; Martínez, A.; Olivas, J.; Sattler, A.; Sánchez-Delgado, R.A.; Maldonado, R.A. Metal-drug synergy: New ruthenium(II) complexes of ketoconazole are highly active against Leishmania major and Trypanosoma cruzi and nontoxic to human or murine normal cells. Eur. J. Biochem., 2013, 18(7), 779-790.
[http://dx.doi.org/10.1007/s00775-013-1024-2] [PMID: 23881220]
[46]
Rodriguez Arce, E.; Sarniguet, C.; Moraes, T.S.; Vieites, M.; Tomaz, A.I.; Medeiros, A.; Comini, M.A.; Varela, J.; Cerecetto, H.; Gonzalez, M.; Marques, F.; García, M.H.; Otero, L.; Gambino, D. A new ruthenium cyclopentadienyl azole compound with activity on tumor cell lines and trypanosomatid parasites. J. Coord. Chem., 2015, 68(16), 2923-2937.
[http://dx.doi.org/10.1080/00958972.2015.1062480]
[47]
Toledo, J.C.; Neto, B.D.; Franco, D.W. Mutual effects in the chemical properties of the ruthenium metal center and ancillary ligands upon coordination. Coord. Chem. Rev., 2005, 249(3-4), 419-431.
[http://dx.doi.org/10.1016/j.ccr.2004.09.016]
[48]
Silva, J.J.; Osakabe, A.L.; Pavanelli, W.R.; Silva, J.S.; Franco, D.W. In vitro and in vivo antiproliferative and trypanocidal activities of ruthenium NO donors. Br. J. Pharmacol., 2007, 152(1), 112-121.
[http://dx.doi.org/10.1038/sj.bjp.0707363] [PMID: 17603548]
[49]
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]
[50]
Silva, J.J.; Guedes, P.M.; Zottis, A.; Balliano, T.L.; Nascimento Silva, F.O.; França Lopes, L.G.; Ellena, J.; Oliva, G.; Andricopulo, A.D.; Franco, D.W.; Silva, J.S. Novel ruthenium complexes as potential drugs for Chagas’s disease: Enzyme inhibition and in vitro/in vivo trypanocidal activity. Br. J. Pharmacol., 2010, 160(2), 260-269.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00524.x] [PMID: 20105182]
[51]
Hartinger, C.G.; Zorbas-Seifried, S.; Jakupec, M.A.; Kynast, B.; Zorbas, H.; Keppler, B.K. From bench to bedside-preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A). J. Inorg. Biochem., 2006, 100(5-6), 891-904.
[http://dx.doi.org/10.1016/j.jinorgbio.2006.02.013] [PMID: 16603249]
[52]
Anitha, P.; Chitrapriya, N.; Jang, Y.J.; Viswanathamurthi, P. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity of new ruthenium(II) complexes of thiosemicarbazone/semicarbazone bearing 9,10-phenanthrenequinone. J. Photochem. Photobiol. B, 2013, 129, 17-26.
[http://dx.doi.org/10.1016/j.jphotobiol.2013.09.005] [PMID: 24144689]
[53]
Demoro, B.; Rossi, M.; Caruso, F.; Liebowitz, D.; Olea-Azar, C.; Kemmerling, U.; Maya, J.D.; Guiset, H.; Moreno, V.; Pizzo, C.; Mahler, G.; Otero, L.; Gambino, D. Potential mechanism of the anti-trypanosomal activity of organoruthenium complexes with bioactive thiosemicarbazones. Biol. Trace Elem. Res., 2013, 153(1-3), 371-381.
[http://dx.doi.org/10.1007/s12011-013-9653-4] [PMID: 23564472]
[54]
Bergamo, A.; Gaiddon, C.; Schellens, J.H.; Beijnen, J.H.; Sava, G. Approaching tumour therapy beyond platinum drugs: Status of the art and perspectives of ruthenium drug candidates. J. Inorg. Biochem., 2012, 106(1), 90-99.
[http://dx.doi.org/10.1016/j.jinorgbio.2011.09.030] [PMID: 22112845]
[55]
Gambino, D.; Otero, L. Perspectives on what ruthenium-based compounds could offer in the development of potential antiparasitic drugs. Inorg. Chim. Acta, 2012, 393, 103-114.
[http://dx.doi.org/10.1016/j.ica.2012.05.028]
[56]
Otero, L.; Smircich, P.; Vieites, M.; Ciganda, M.; Severino, P.C.; Terenzi, H.; Cerecetto, H.; Gambino, D.; Garat, B. DNA conformational changes and cleavage by ruthenium(II) nitrofurylsemicarbazone complexes. J. Inorg. Biochem., 2007, 101(1), 74-79.
[http://dx.doi.org/10.1016/j.jinorgbio.2006.08.004] [PMID: 17027974]
[57]
Miserachs, H.G.; Cipriani, M.; Grau, J.; Vilaseca, M.; Lorenzo, J.; Medeiros, A.; Comini, M.A.; Gambino, D.; Otero, L.; Moreno, V. Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands. J. Inorg. Biochem., 2015, 150, 38-47.
[http://dx.doi.org/10.1016/j.jinorgbio.2015.06.007] [PMID: 26079954]
[58]
Ong, Y.C.; Gasser, G. Organometallic compounds in drug discovery: Past, present and future. Drug Discov. Today. Technol., 2019, 37, 117-124.
[PMID: 34895650]
[59]
de Souza, W.; Rodrigues, J.C. Sterol biosynthesis pathway as target for anti-trypanosomatid drugs. Interdiscip. Perspect. Infect. Dis., 2009, 2009, 642502.
[http://dx.doi.org/10.1155/2009/642502] [PMID: 19680554]
[60]
Demoro, B.; Sarniguet, C.; Sánchez-Delgado, R.; Rossi, M.; Liebowitz, D.; Caruso, F.; Olea-Azar, C.; Moreno, V.; Medeiros, A.; Comini, M.A.; Otero, L.; Gambino, D. New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: Potential anti-trypanosomal agents. Dalton Trans., 2012, 41(5), 1534-1543.
[http://dx.doi.org/10.1039/C1DT11519G] [PMID: 22138896]
[61]
Costa, M.S.; Gonçalves, Y.G.; Nunes, D.C.O.; Napolitano, D.R.; Maia, P.I.S.; Rodrigues, R.S.; Rodrigues, V.M.; Von Poelhsitz, G.; Yoneyama, K.A.G. Anti-Leishmania activity of new ruthenium(II) complexes: Effect on parasite-host interaction. J. Inorg. Biochem., 2017, 175, 225-231.
[http://dx.doi.org/10.1016/j.jinorgbio.2017.07.023] [PMID: 28783554]
[62]
Sabzevari, S.; Mohebali, M.; Hashemi, S.A. Mucosal and mucocutaneous leishmaniasis in Iran from 1968 to 2018: A narrative review of clinical features, treatments, and outcomes. Int. J. Dermatol., 2020, 59(5), 606-612.
[http://dx.doi.org/10.1111/ijd.14762] [PMID: 31943166]
[63]
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]
[64]
Marcusso Orsini, T; Kawakami, NY; Panis, C; Fortes dos Santos Thomazelli, AP; Tomiotto-Pellissier, F; Cataneo, AH; Kian, D; Megumi Yamauchi, L; Gouveia, FS, Junior; de França Lopes, LG; Cecchini, R Antileishmanial activity and inducible nitric oxide synthase activation by RuNO complex. Mediators Inflamm., 2016.
[http://dx.doi.org/10.1155/2016/2631625]
[65]
Zaki, M.; Hairat, S.; Aazam, E.S. Scope of organometallic compounds based on transition metal-arene systems as anticancer agents: Starting from the classical paradigm to targeting multiple strategies. RSC Advances, 2019, 9(6), 3239-3278.
[http://dx.doi.org/10.1039/C8RA07926A]
[66]
Marković, K.; Milačič, R.; Marković, S.; Kladnik, J.; Turel, I.; Ščančar, J. Binding kinetics of ruthenium pyrithione chemotherapeutic candidates to human serum proteins studied by HPLC-ICP-MS. Molecules, 2020, 25(7), 1512.
[http://dx.doi.org/10.3390/molecules25071512] [PMID: 32225069]
[67]
Van Assche, T.; Deschacht, M.; da Luz, R.A.; Maes, L.; Cos, P. Leishmania-macrophage interactions: Insights into the redox biology. Free Radic. Biol. Med., 2011, 51(2), 337-351.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.011] [PMID: 21620959]
[68]
Colina-Vegas, L.; Godinho, J.L.; Coutinho, T.; Correa, R.S.; de Souza, W.; Rodrigues, J.C.; Batista, A.A.; Navarro, M. Antiparasitic activity and ultrastructural alterations provoked by organoruthenium complexes against Leishmania amazonensis. New J. Chem., 2019, 43(3), 1431-1439.
[http://dx.doi.org/10.1039/C8NJ04657C]
[69]
Toledano-Magaña, Y.; García-Ramos, J.C.; Torres-Gutiérrez, C.; Vázquez-Gasser, C.; Esquivel-Sánchez, J.M.; Flores-Alamo, M.; Ortiz-Frade, L.; Galindo-Murillo, R.; Nequiz, M.; Gudiño-Zayas, M.; Laclette, J.P.; Carrero, J.C.; Ruiz-Azuara, L. Water-soluble ruthenium (II) chiral heteroleptic complexes with amoebicidal in vitro and in vivo activity. J. Med. Chem., 2017, 60(3), 899-912.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00795] [PMID: 28075589]
[70]
Cedillo-Gutiérrez, E.L.; Hernández-Ayala, L.F.; Torres-Gutiérrez, C.; Reina, M.; Flores-Alamo, M.; Carrero, J.C.; Ugalde-Saldívar, V.M.; Ruiz-Azuara, L. Identification of descriptors for structure-activity relationship in ruthenium (II) mixed compounds with antiparasitic activity. Eur. J. Med. Chem., 2020, 189, 112084.
[http://dx.doi.org/10.1016/j.ejmech.2020.112084] [PMID: 32000049]
[71]
Athar, F.; Husain, K.; Abid, M.; Agarwal, S.M.; Coles, S.J.; Hursthouse, M.B.; Maurya, M.R.; Azam, A. Synthesis and anti-amoebic activity of gold(I), ruthenium(II), and copper(II) complexes of metronidazole. Chem. Biodivers., 2005, 2(10), 1320-1330.
[http://dx.doi.org/10.1002/cbdv.200590104] [PMID: 17191933]
[72]
Nagaraja, S.; Ankri, S. Target identification and intervention strategies against amebiasis. Drug Resist. Updat., 2019, 44, 1-14.
[http://dx.doi.org/10.1016/j.drup.2019.04.003] [PMID: 31112766]
[73]
Tyebji, S.; Seizova, S.; Hannan, A.J.; Tonkin, C.J. Toxoplasmosis: A pathway to neuropsychiatric disorders. Neurosci. Biobehav. Rev., 2019, 96, 72-92.
[http://dx.doi.org/10.1016/j.neubiorev.2018.11.012] [PMID: 30476506]
[74]
Kanatani, S.; Fuks, J.M.; Olafsson, E.B.; Westermark, L.; Chambers, B.; Varas-Godoy, M.; Uhlén, P.; Barragan, A. Voltage-dependent calcium channel signaling mediates GABAA receptor-induced migratory activation of dendritic cells infected by Toxoplasma gondii. PLoS Pathog., 2017, 13(12), e1006739.
[http://dx.doi.org/10.1371/journal.ppat.1006739] [PMID: 29216332]
[75]
Weidner, J.M.; Kanatani, S.; Uchtenhagen, H.; Varas-Godoy, M.; Schulte, T.; Engelberg, K.; Gubbels, M.J.; Sun, H.S.; Harrison, R.E.; Achour, A.; Barragan, A. Migratory activation of parasitized dendritic cells by the protozoan Toxoplasma gondii 14-3-3 protein. Cell. Microbiol., 2016, 18(11), 1537-1550.
[http://dx.doi.org/10.1111/cmi.12595] [PMID: 27018989]
[76]
Konradt, C.; Ueno, N.; Christian, D.A.; Delong, J.H.; Pritchard, G.H.; Herz, J.; Bzik, D.J.; Koshy, A.A.; McGavern, D.B.; Lodoen, M.B.; Hunter, C.A. Endothelial cells are a replicative niche for entry of Toxoplasma gondii to the central nervous system. Nat. Microbiol., 2016, 1(3), 16001.
[http://dx.doi.org/10.1038/nmicrobiol.2016.1] [PMID: 27572166]
[77]
Hopper, A.T.; Brockman, A.; Wise, A.; Gould, J.; Barks, J.; Radke, J.B.; Sibley, L.D.; Zou, Y.; Thomas, S. Discovery of selective Toxoplasma gondii dihydrofolate reductase inhibitors for the treatment of toxoplasmosis. J. Med. Chem., 2019, 62(3), 1562-1576.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01754] [PMID: 30624926]
[78]
Sharma, M.; Chauhan, P.M. Dihydrofolate reductase as a therapeutic target for infectious diseases: Opportunities and challenges. Future Med. Chem., 2012, 4(10), 1335-1365.
[http://dx.doi.org/10.4155/fmc.12.68] [PMID: 22800373]
[79]
Alday, P.H.; Doggett, J.S. Drugs in development for toxoplasmosis: Advances, challenges, and current status. Drug Des. Devel. Ther., 2017, 11, 273-293.
[http://dx.doi.org/10.2147/DDDT.S60973] [PMID: 28182168]
[80]
Robert-Gangneux, F.; Dardé, M.L. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin. Microbiol. Rev., 2012, 25(2), 264-296.
[http://dx.doi.org/10.1128/CMR.05013-11] [PMID: 22491772]
[81]
Barna, F.; Debache, K.; Vock, C.A.; Küster, T.; Hemphill, A. In vitro effects of novel ruthenium complexes in Neospora caninum and Toxoplasma gondii tachyzoites. Antimicrob. Agents Chemother., 2013, 57(11), 5747-5754.
[http://dx.doi.org/10.1128/AAC.02446-12] [PMID: 23979747]
[82]
Basto, A.P.; Müller, J.; Rubbiani, R.; Stibal, D.; Giannini, F.; Süss-Fink, G.; Balmer, V.; Hemphill, A.; Gasser, G.; Furrer, J. Characterization of the activities of dinuclear thiolato-bridged arene ruthenium complexes against Toxoplasma gondii. Antimicrob. Agents Chemother., 2017, 61(9), e01031-e17.
[http://dx.doi.org/10.1128/AAC.01031-17] [PMID: 28652238]
[83]
Bouzaidi-Tiali, N.; Aeby, E.; Charrière, F.; Pusnik, M.; Schneider, A. Elongation factor 1a mediates the specificity of mitochondrial tRNA import in T. brucei. EMBO J., 2007, 26(20), 4302-4312.
[http://dx.doi.org/10.1038/sj.emboj.7601857] [PMID: 17853889]
[84]
Esseiva, A.C.; Naguleswaran, A.; Hemphill, A.; Schneider, A. Mitochondrial tRNA import in Toxoplasma gondii. J. Biol. Chem., 2004, 279(41), 42363-42368.
[http://dx.doi.org/10.1074/jbc.M404519200] [PMID: 15280394]
[85]
Wang, S.; Zhang, Z.; Wang, Y.; Gadahi, J.A.; Xu, L.; Yan, R.; Song, X.; Li, X. Toxoplasma gondii elongation factor 1-alpha (TgEF-1α) is a novel vaccine candidate antigen against toxoplasmosis. Front. Microbiol., 2017, 8, 168.
[http://dx.doi.org/10.3389/fmicb.2017.00168] [PMID: 28243226]
[86]
Gupta, S.; Bhandari, Y.P.; Reddy, M.V.; Harinath, B.C.; Rathaur, S. Setaria cervi: Immunoprophylactic potential of glutathione-S-transferase against filarial parasite Brugia malayi. Exp. Parasitol., 2005, 109(4), 252-255.
[http://dx.doi.org/10.1016/j.exppara.2004.12.003] [PMID: 15755423]
[87]
Chandra, S.; Ruhela, D.; Deb, A.; Vishwakarma, R.A. Glycobiology of the Leishmania parasite and emerging targets for antileishmanial drug discovery. Expert Opin. Ther. Targets, 2010, 14(7), 739-757.
[http://dx.doi.org/10.1517/14728222.2010.495125] [PMID: 20536412]
[88]
Boscá, L.; Zeini, M.; Través, P.G.; Hortelano, S. Nitric oxide and cell viability in inflammatory cells: A role for NO in macrophage function and fate. Toxicology, 2005, 208(2), 249-258.
[http://dx.doi.org/10.1016/j.tox.2004.11.035] [PMID: 15691589]
[89]
Pavanelli, W.R.; da Silva, J.J.; Panis, C.; Cunha, T.M.; de Abreu Oliveira, F.J.; de Menezes, M.C.; Costa, I.C.; da Silva Thomé, G.; da Silva, F.O.; de Sousa, E.H.; de França Lopes, L.G. Nitric oxide donors with therapeutic strategic in experimental schistossomiasis mansoni. Am. J. Immunol., 2014, 10(4), 225-239.
[http://dx.doi.org/10.3844/ajisp.2014.225.239]
[90]
Sundaraneedi, M.K.; Tedla, B.A.; Eichenberger, R.M.; Becker, L.; Pickering, D.; Smout, M.J.; Rajan, S.; Wangchuk, P.; Keene, F.R.; Loukas, A.; Collins, J.G.; Pearson, M.S. Polypyridylruthenium(II) complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases. PLoS Negl. Trop. Dis., 2017, 11(12), e0006134.
[http://dx.doi.org/10.1371/journal.pntd.0006134] [PMID: 29240773]
[91]
Ruano, A.L.; López-Abán, J.; Fernández-Soto, P.; de Melo, A.L.; Muro, A. Treatment with nitric oxide donors diminishes hyperinfection by Strongyloides venezuelensis in mice treated with dexamethasone. Acta Trop., 2015, 152, 90-95.
[http://dx.doi.org/10.1016/j.actatropica.2015.08.019] [PMID: 26342794]
[92]
Pullan, R.L.; Smith, J.L.; Jasrasaria, R.; Brooker, S.J. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasit. Vectors, 2014, 7(1), 37.
[http://dx.doi.org/10.1186/1756-3305-7-37] [PMID: 24447578]
[93]
Vyas, N.A.; Bhat, S.S.; Kumbhar, A.S.; Sonawane, U.B.; Jani, V.; Joshi, R.R.; Ramteke, S.N.; Kulkarni, P.P.; Joshi, B. Ruthenium(II) polypyridyl complex as inhibitor of acetylcholinesterase and Aβ aggregation. Eur. J. Med. Chem., 2014, 75, 375-381.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.052] [PMID: 24556150]
[94]
Sundaraneedi, M.; Eichenberger, R.M.; Al-Hallaf, R.; Yang, D.; Sotillo, J.; Rajan, S.; Wangchuk, P.; Giacomin, P.R.; Keene, F.R.; Loukas, A.; Collins, J.G.; Pearson, M.S. Polypyridylruthenium(II) complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases. Int. J. Parasitol. Drugs Drug Resist., 2018, 8(1), 1-7.
[http://dx.doi.org/10.1016/j.ijpddr.2017.11.005] [PMID: 29207309]
[95]
Klementowicz, J.E.; Travis, M.A.; Grencis, R.K. Trichuris muris: A model of gastrointestinal parasite infection. Semin. Immunopathol., 2012, 34(6), 815-828.
[http://dx.doi.org/10.1007/s00281-012-0348-2] [PMID: 23053395]

Rights & Permissions Print Cite
Article Metrics
40
1
© 2024 Bentham Science Publishers | Privacy Policy