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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Review Article

Structural-activity Relationship of Metallo-aminoquines as Next Generation Antimalarials

Author(s): Mohammad Abid, Shailja Singh, Timothy J. Egan and Mukesh C. Joshi*

Volume 22, Issue 6, 2022

Published on: 31 January, 2022

Page: [436 - 472] Pages: 37

DOI: 10.2174/1568026622666220105103751

Price: $65


Apicomplexian parasite of the genus Plasmodium is the causative agent of malaria, one of the most devastating, furious and common infectious disease throughout the world. According to the latest World malaria report, there were 229 million cases of malaria in 2019 majorly consist of children under 5 years of age. Some of known analogues viz. quinine, quinoline-containing compounds have been used for last century in the clinical treatment of malaria. Past few decades witnessed the emergence of multi-drug resistance (MDR) strains of Plasmodium species to existing antimalarials pressing the need for new drug candidates. Thus, in those decades bioorganometallic approach to malaria therapy has been introduced which led to the discovery of noval metalcontaining aminoquinolines analogues viz. ferroquine (FQ or 1), Ruthenoquine (RQ or 2) and other related potent metalanalogues. It observed that some metal containing analogues (Fe-, Rh-, Ru-, Re-, Au-, Zn-, Cr-, Pd-, Sn-, Cd-, Ir-, Co-, Cu-, and Mn-aminoquines) were more potent; however, some were equally potent as Chloroquine (CQ) and 1. This is probably due to the intertion of metals in the CQ via various approaches, which might be a very attractive strategy to develop a SAR of novel metal containing antimalarials. Thus, this review aim to summarize the SAR of metal containing aminoquines towards the discovery of potent antimalarial hybrids to provide an insight for rational designs of more effective and less toxic metal containing amonoquines.

Keywords: Chloroquine, Ferroquine, Aminoquinolines, Antimalarial, In vitro, In vivo, Cytotoxicity, β-Hematin inhibition.

Graphical Abstract
Gasser, G.; Metzler-Nolte, N. The potential of organometallic complexes in medicinal chemistry. Curr. Opin. Chem. Biol., 2012, 16(1-2), 84-91.
[] [PMID: 22366385]
Chavain, N.; Biot, C. Organometallic complexes: new tools for chemotherapy. Curr. Med. Chem., 2010, 17(25), 2729-2745.
[] [PMID: 20586720]
Jaouen, G.; Metzler-Nolte, N. Eds.; Medicinal Organometallic Chemistry; Topics in Organometallic Chemistry; Springer: Berlin, , 2010; 32, pp. 1-291.
Biot, C.; Castro, W.; Botté, C.Y.; Navarro, M. The therapeutic potential of metal-based antimalarial agents: implications for the mechanism of action. Dalton Trans., 2012, 41(21), 6335-6349.
[] [PMID: 22362072]
García-Barrantes, P.M.; Lamoureux, G.V.; Pérez, A.L.; García-Sánchez, R.N.; Martínez, A.R.; San Feliciano, A. Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents. Eur. J. Med. Chem., 2013, 70, 548-557.
[] [PMID: 24211630]
Kitagawa, T.; Matsumoto, A.; Terashima, I.; Uesono, Y. Antimalarial quinacrine and chloroquine lose their activity by decreasing cationic amphiphilic structure with a slight decrease in pH. J. Med. Chem., 2021, 64(7), 3885-3896.
[] [PMID: 33775096]
Egan, T.J. Quinoline antimalarials. Expert Opin. Ther. Pat., 2001, 11, 185-209.
Talisuna, A.O.; Bloland, P.; D’Alessandro, U. History, dynamics, and public health importance of malaria parasite resistance. Clin. Microbiol. Rev., 2004, 17(1), 235-254.
[] [PMID: 14726463]
Joshi, M.C.; Egan, T.J. Quinoline containing side-chain antimalarial analogs: Recent advances and therapeutic application. Curr. Top. Med. Chem., 2020, 20(8), 617-697.
[] [PMID: 31985377]
Riegel, B.; Roepe, P.D. Altered drug transport by Plasmodium falciparum chloroquine resistance transporter isoforms harboring mutations associated with piperaquine resistance. Biochemistry, 2020, 59(27), 2484-2493.
[] [PMID: 32589406]
Sullivan, D.J., Jr; Gluzman, I.Y., Jr; Russell, D.G.; Goldberg, D.E. On the molecular mechanism of chloroquine’s antimalarial action. Proc. Natl. Acad. Sci. USA, 1996, 93(21), 11865-11870.
[] [PMID: 8876229]
Egan, T.J.; Marques, H.M. The role of haem in the activity of chloroquine and related antimalarial drugs. Coord. Chem. Rev., 1999, 190-192, 493-517.
Wendt, C.; de Souza, W.; Pinheiro, A.; Silva, L.; de Sa Pinheiro, A.A.; Gauvin, R.; Miranda, K. High-resolution electron microscopy analysis of malaria hemozoin crystals reveals new aspects of crystal growth and elemental composition. Cryst. Growth Des., 2021, 21, 5521-5533.
Weinberg, E.D.; Moon, J. Malaria and iron: history and review. Drug Metab. Rev., 2009, 41(4), 644-662.
[] [PMID: 19764831]
Navarro, M.; Gabbiani, C.; Messori, L.; Gambino, D. Metal-based drugs for malaria, trypanosomiasis and leishmaniasis: recent achievements and perspectives. Drug Discov. Today, 2010, 15(23-24), 1070-1078.
[] [PMID: 20974285]
Sánchez-Delgado, R.A.; Anzellotti, A. Metal complexes as chemotherapeutic agents against tropical diseases: trypanosomiasis, malaria and leishmaniasis. Mini Rev. Med. Chem., 2004, 4(1), 23-30.
[] [PMID: 14754440]
Sharma, V.; Piwnica-Worms, D. Metal complexes for therapy and diagnosis of drug resistance. Chem. Rev., 1999, 99(9), 2545-2560.
[] [PMID: 11749491]
Sharma, V. Therapeutic drugs for targeting chloroquine resistance in malaria. Mini Rev. Med. Chem., 2005, 5(4), 337-351.
[] [PMID: 15853624]
Biot, C.; Glorian, G.; Maciejewski, L.A.; Brocard, J.S. Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue. J. Med. Chem., 1997, 40(23), 3715-3718.
[] [PMID: 9371235]
Biot, C.; Chibale, K. Novel approaches to antimalarial drug discovery. Infect. Disord. Drug Targets, 2006, 6(2), 173-204.
[] [PMID: 16789878]
Biot, C.; Chavain, N.; Dubar, F.; Pradines, B.; Trivelli, X.; Brocard, J.; Forfar, I.; Dive, D. Structure activity relationships of 4-N-substituted ferroquine analogues: Timeto re-evaluate the mechanism of action of ferroquine. J. Organomet. Chem., 2009, 694(6), 845-854.
Kapishnikov, S.; Staalsø, T.; Yang, Y.; Lee, J.; Pérez-Berná, A.J.; Pereiro, E.; Yang, Y.; Werner, S.; Guttmann, P.; Leiserowitz, L.; Als-Nielsen, J. Mode of action of quinoline antimalarial drugs in red blood cells infected by Plasmodium falciparum revealed in vivo. Proc. Natl. Acad. Sci. USA, 2019, 116(46), 22946-22952.
[PMID: 31659055]
Sharma, B.; Kumar, V. Has ferrocene really delivered its role in accentuating the bioactivity of organic scaffolds? J. Med. Chem., 2021, 64(23), 16865-16921.
[] [PMID: 34792350]
Payen, O.; Top, S.; Vessières, A.; Brulé, E.; Plamont, M-A.; McGlinchey, M.J.; Müller-Bunz, H.; Jaouen, G. Synthesis and structure-activity relationships of the first ferrocenyl-aryl-hydantoin derivatives of the nonsteroidal antiandrogen nilutamide. J. Med. Chem., 2008, 51(6), 1791-1799.
[] [PMID: 18303829]
Peter, S.; Aderibigbe, B.A. Ferrocene-based compounds with antimalaria/anticancer activity. Molecules, 2019, 24(19), 3604.
[] [PMID: 31591298]
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.
[] [PMID: 8676344]
Navarro, M.; Pérez, H.; Sánchez-Delgado, R.A. Toward a novel metal-based chemotherapy against tropical diseases. 3. Synthesis and antimalarial activity in vitro and in vivo of the new gold-chloroquine complex [Au(PPh3)(CQ)]PF6. J. Med. Chem., 1997, 40(12), 1937-1939.
[] [PMID: 9191972]
Navarro, M.; Castro, W.; Martínez, A.; Sánchez Delgado, R.A. The mechanism of antimalarial action of [Au(CQ)(PPh(3))]PF(6): structural effects and increased drug lipophilicity enhance heme aggregation inhibition at lipid/water interfaces. J. Inorg. Biochem., 2011, 105(2), 276-282.
[] [PMID: 21194628]
Biot, C.; Daher, W.; Chavain, N.; Fandeur, T.; Khalife, J.; Dive, D.; De Clercq, E. Design and synthesis of hydroxyferroquine derivatives with antimalarial and antiviral activities. J. Med. Chem., 2006, 49(9), 2845-2849.
[] [PMID: 16640347]
Dondorp, A.M.; Nosten, F.; Yi, P.; Das, D.; Phyo, A.P.; Tarning, J.; Lwin, K.M.; Ariey, F.; Hanpithakpong, W.; Lee, S.J.; Ringwald, P.; Silamut, K.; Imwong, M.; Chotivanich, K.; Lim, P.; Herdman, T.; An, S.S.; Yeung, S.; Singhasivanon, P.; Day, N.P.J.; Lindegardh, N.; Socheat, D.; White, N.J. Artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med., 2009, 361(5), 455-467.
[] [PMID: 19641202]
Taylor, S.M.; Juliano, J.J.; Meshnick, S.R. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N. Engl. J. Med., 2018, 378(18), 1671-1680.
[] [PMID: 29668352]
Dechy-Cabaret, O.; Benoit-Vical, F.; Robert, A.; Meunier, B. Preparation and antimalarial activities of “trioxaquines”, new modular molecules with a trioxane skeleton linked to a 4-aminoquinoline. ChemBioChem, 2000, 1(4), 281-283.
[<281:AID-CBIC281>3.0.CO;2-W] [PMID: 11828420]
Robert, A.; Dechy-Cabaret, O.; Cazelles, J.; Meunier, B. From mechanistic studies on artemisinin derivatives to new modular antimalarial drugs. Acc. Chem. Res., 2002, 35(3), 167-174.
[] [PMID: 11900520]
Walsh, J.J.; Bell, A. Hybrid drugs for malaria. Curr. Pharm. Des., 2009, 15(25), 2970-2985.
[] [PMID: 19754373]
Cavalli, A.; Bolognesi, M.L. Neglected tropical diseases: multi-target-directed ligands in the search for novel lead candidates against Trypanosoma and Leishmania. J. Med. Chem., 2009, 52(23), 7339-7359.
[] [PMID: 19606868]
Dubar, F.; Khalife, J.; Brocard, J.; Dive, D.; Biot, C. Ferroquine, an ingenious antimalarial drug: thoughts on the mechanism of action. Molecules, 2008, 13(11), 2900-2907.
[] [PMID: 19020475]
Domarle, O.; Blampain, G.; Agnaniet, H.; Nzadiyabi, T.; Lebibi, J.; Brocard, J.; Maciejewski, L.; Biot, C.; Georges, A.J.; Millet, P. In vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine. Antimicrob. Agents Chemother., 1998, 42(3), 540-544.
[] [PMID: 9517929]
Bellot, F.; Coslédan, F.; Vendier, L.; Brocard, J.; Meunier, B.; Robert, A. Trioxaferroquines as new hybrid antimalarial drugs. J. Med. Chem., 2010, 53(10), 4103-4109.
[] [PMID: 20443628]
Salas, P.F.; Herrmann, C.; Cawthray, J.F.; Nimphius, C.; Kenkel, A.; Chen, J.; de Kock, C.; Smith, P.J.; Patrick, B.O.; Adam, M.J.; Orvig, C. Structural characteristics of chloroquine-bridged ferrocenophane analogues of ferroquine may obviate malaria drug-resistance mechanisms. J. Med. Chem., 2013, 56(4), 1596-1613.
[] [PMID: 23327489]
Biot, C.; Taramelli, D.; Forfar-Bares, I.; Maciejewski, L.A.; Boyce, M.; Nowogrocki, G.; Brocard, J.S.; Basilico, N.; Olliaro, P.; Egan, T.J. Insights into the mechanism of action of ferroquine. Relationship between physicochemical properties and antiplasmodial activity. Mol. Pharm., 2005, 2(3), 185-193.
[] [PMID: 15934779]
Scovill, J.P.; Klayman, D.L.; Lambros, C.; Childs, G.E.; Notsch, J.D.J. 2-Acetylpyridine thiosemicarbazones. 9. Derivatives of 2-acetylpyridine 1-oxide as potential antimalarial agents. J. Med. Chem., 1984, 27(1), 87-91.
[] [PMID: 6361258]
Ames, J.R.; Ryan, M.D.; Klayman, D.L.; Kovacic, P. Charge transfer and oxy radicals in antimalarial action. Quinones, dapsone metabolites, metal complexes, iminium ions, and peroxides. J. Free Radic. Biol. Med., 1985, 1(5-6), 353-361.
[] [PMID: 3837802]
Klayman, D.L.; Acton, N.; Scovill, J.P. 2-Acetylpyridine thiosemicarbazones. 12. Derivatives of 3-acetylisoquinoline as potential antimalarial agents. Arzneimittelforschung, 1986, 36(1), 10-13.
[] [PMID: 3513773]
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.
[] [PMID: 15163200]
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.
[] [PMID: 17052908]
Biot, C.; Pradines, B.; Sergeant, M.H.; Gut, J.; Rosenthal, P.J.; Chibale, K. Design, synthesis, and antimalarial activity of structural chimeras of thiosemicarbazone and ferroquine analogues. Bioorg. Med. Chem. Lett., 2007, 17(23), 6434-6438.
[] [PMID: 17949976]
Muganza, F.M. Ferrocenic metal chelators: synthesis biological and elechochemical studies master dissertations, departments of chemistry; University of Cape Town, 2006.
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.
[] [PMID: 3053784]
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.
[] [PMID: 12499184]
Chiyanzu, I.; Clarkson, C.; Smith, P.J.; Lehman, J.; Gut, J.; Rosenthal, P.J.; Chibale, K. Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives. Bioorg. Med. Chem., 2005, 13(9), 3249-3261.
[] [PMID: 15809160]
Biot, C.; Daher, W.; Ndiaye, C.M.; Melnyk, P.; Pradines, B.; Chavain, N.; Pellet, A.; Fraisse, L.; Pelinski, L.; Jarry, C.; Brocard, J.; Khalife, J.; Forfar-Bares, I.; Dive, D. Probing the role of the covalent linkage of ferrocene into a chloroquine template. J. Med. Chem., 2006, 49(15), 4707-4714.
[] [PMID: 16854077]
Singh, A.; Rani, A.; Gut, J.; Rosenthal, P.J.; Kumar, V. Piperazine-linked 4-aminoquinoline-chalcone/ferrocenyl-chalcone conjugates: Synthesis and antiplasmodial evaluation. Chem. Biol. Drug Des., 2017, 90(4), 590-595.
[] [PMID: 28332319]
Raj, R.; Saini, A.; Gut, J.; Rosenthal, P.J.; Kumar, V. Synthesis and in vitro antiplasmodial evaluation of 7-chloroquinoline-chalcone and 7-chloroquinoline-ferrocenylchalcone conjugates. Eur. J. Med. Chem., 2015, 95, 230-239.
[] [PMID: 25817773]
Singh, A.; Gut, J.; Rosenthal, P.J.; Kumar, V. 4-Aminoquinoline-ferrocenyl-chalcone conjugates: Synthesis and anti-plasmodial evaluation. Eur. J. Med. Chem., 2017, 125, 269-277.
[] [PMID: 27688182]
Herrmann, C.; Salas, P.F.; Patrick, B.O.; de Kock, C.; Smith, P.J.; Adam, M.J.; Orvig, C. 1,2-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarial agents. Dalton Trans., 2012, 41(21), 6431-6442.
[] [PMID: 22378031]
Atteke, C.; Ndong, J.M.M.; Aubouy, A.; Maciejewski, L.; Brocard, J.; Lébibi, J.; Deloron, P. In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooué region of Gabon. J. Antimicrob. Chemother., 2003, 51(4), 1021-1024.
[] [PMID: 12654770]
Chavain, N.; Davioud-Charvet, E.; Trivelli, X.; Mbeki, L.; Rottmann, M.; Brun, R.; Biot, C. Antimalarial activities of ferroquine conjugates with either glutathione reductase inhibitors or glutathione depletors via a hydrolyzable amide linker. Bioorg. Med. Chem., 2009, 17(23), 8048-8059.
[] [PMID: 19864147]
Bauer, H.; Fritz-Wolf, K.; Winzer, A.; Kuhner, S.; Little, S.; Yardley, V.; Vezin, H.; Palfey, B.; Schirmer, R.H.; Davioud-Charvet, E. A fluoro analogue of the menadione derivative 6-[2‘-(3‘-Methyl)-1‘,4‘-naphthoquinolyl]hexanoic acid is a suicide substrate of glutathione reductase. Crystal structure of the alkylated human enzyme. J. Am. Chem. Soc., 2006, 128(33), 10784-10794.
[] [PMID: 16910673]
Biot, C.; Bauer, H.; Schirmer, R.H.; Davioud-Charvet, E. 5-substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. J. Med. Chem., 2004, 47(24), 5972-5983.
[] [PMID: 15537352]
Wenzel, N.I.; Chavain, N.; Wang, Y.; Friebolin, W.; Maes, L.; Pradines, B.; Lanzer, M.; Yardley, V.; Brun, R.; Herold-Mende, C.; Biot, C.; Tóth, K.; Davioud-Charvet, E. Antimalarial versus cytotoxic properties of dual drugs derived from 4-aminoquinolines and Mannich bases: interaction with DNA. J. Med. Chem., 2010, 53(8), 3214-3226.
[] [PMID: 20329733]
Musonda, C.C.; Yardley, V.; de Souza, R.C.C.; Ncokazi, K.; Egan, T.J.; Chibale, K. Antiplasmodial, β-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines. Org. Biomol. Chem., 2008, 6(23), 4446-4451.
[] [PMID: 19005606]
Beagley, P.; Blackie, M.A.L.; Chibale, K.; Clarkson, C.; Meijboom, R.; Moss, J.R.; Smith, P.J.; Su, H. Synthesis and antiplasmodial activity in vitro of new ferrocene-chloroquine analogues. Dalton Trans., 2003, 15, 3046-3051.
Beagley, P.; Blackie, M.L.A.; Chibale, K.; Clarkson, C.; Meijboom, R.; Moss, J.R.; Smith, P.J. Synthesis and antiplasmodial activity in vitro of new ruthenocene-chloroquine analogues. J. Chem. Soc., Dalton Trans., 2002, 23, 4426-4433.
Stringer, T.; Wiesner, L.; Smith, G.S. Ferroquine-derived polyamines that target resistant Plasmodium falciparum. Eur. J. Med. Chem., 2019, 179, 78-83.
[] [PMID: 31238252]
Minić, A.; Van de Walle, T.; Van Hecke, K.; Combrinck, J.; Smith, P.J.; Chibale, K.; D’hooghe, M. Design and synthesis of novel ferrocene-quinoline conjugates and evaluation of their electrochemical and antiplasmodium properties. Eur. J. Med. Chem., 2020, 187111963
[] [PMID: 31865015]
Ibrahim, S.; Tagami, T.; Ozeki, T. Effective-loading of Platinum-Chloroquine into PEGylated neutral and cationic liposomes as a drug delivery system for resistant malaria parasites. Biol. Pharm. Bull., 2017, 40(6), 815-823.
[] [PMID: 28566625]
de Souza, N.B.; Carmo, A.M.L.; Lagatta, D.C.; Alves, M.J.M.; Fontes, A.P.S.; Coimbra, E.S.; da Silva, A.D.; Abramo, C. 4-aminoquinoline analogues and its platinum (II) complexes as antimalarial agents. Biomed. Pharmacother., 2011, 65(4), 313-316.
[] [PMID: 21704476]
Macedo, T.S.; Villarreal, W.; Couto, C.C.; Moreira, D.R.M.; Navarro, M.; Machado, M.; Prudêncio, M.; Batista, A.A.; Soares, M.B.P. Platinum(ii)-chloroquine complexes are antimalarial agents against blood and liver stages by impairing mitochondrial function. Metallomics, 2017, 9(11), 1548-1561.
[] [PMID: 28960224]
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.
[] [PMID: 26491831]
Ekengard, E.; Kumar, K.; Fogeron, T.; de Kock, C.; Smith, P.J.; Haukka, M.; Monari, M.; Nordlander, E. Pentamethylcyclopentadienyl-rhodium and iridium complexes containing (N^N and N^O) bound chloroquine analogue ligands: synthesis, characterization and antimalarial properties. Dalton Trans., 2016, 45(9), 3905-3917.
[] [PMID: 26829897]
Ekengard, E.; Bergare, I.; Hansson, J.; Doverbratt, I.; Monari, M.; Gordhan, B.; Kana, B.; de Kock, C.; Smith, P.J.; Nordlander, E. A pyrazine amide-4-aminoquinoline hybrid and its Rhodium and Iridium pentamethylcyclopentadienyl complexes; evaluation of anti-mycobacterial and anti-plasmodial activities. J. Mex. Chem. Soc., 2017, 61(2), 158-166.
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.
[] [PMID: 30529881]
Navarro, M.; Pekerar, S.; Perez, H.A. Synthesis, characterization and antimalarial activity of new Iridium-chloroquine complexes. Polyhedron, 2007, 26, 2420-2424.
Martinez, A.; Deregnaucourt, C.; Sinou, V.; Latour, C.; Roy, D.; Schrevel, J.; Sanchez-Delgado, R.A. Synthesis of an organo-Ruthenium aminoquinoline-trioxane hybrid and evaluation of its activity against Plasmodium falciparum and its toxicity toward normal mammalian cells. Med. Chem. Res., 2017, 26(2), 473-483.
Delhaes, L.; Biot, C.; Berry, L.; Delcourt, P.; Maciejewski, L.A.; Camus, D.; Brocard, J.S.; Dive, D. Synthesis of ferroquine enantiomers: first investigation of effects of metallocenic chirality upon antimalarial activity and cytotoxicity. ChemBioChem, 2002, 3(5), 418-423.
[<418:AID-CBIC418>3.0.CO;2-P] [PMID: 12007175]
Briolant, S.; Parola, P.; Fusaï, T.; Madamet-Torrentino, M.; Baret, E.; Mosnier, J.; Delmont, J.P.; Parzy, D.; Minodier, P.; Rogier, C.; Pradines, B. Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium falciparum to chloroquine: requirement of a standardized in vitro assay. Malar. J., 2007, 6(1), 44.
[] [PMID: 17437625]
Marfurt, J.; Chalfein, F.; Prayoga, P.; Wabiser, F.; Kenangalem, E.; Piera, K.A.; Machunter, B.; Tjitra, E.; Anstey, N.M.; Price, R.N. Ex vivo drug susceptibility of ferroquine against chloroquine-resistant isolates of Plasmodium falciparum and P. vivax. Antimicrob. Agents Chemother., 2011, 55(9), 4461-4464.
[] [PMID: 21730116]
Charman, S.A.; Arbe-Barnes, S.; Bathurst, I.C.; Brun, R.; Campbell, M.; Charman, W.N.; Chiu, F.C.K.; Chollet, J.; Craft, J.C.; Creek, D.J.; Dong, Y.; Matile, H.; Maurer, M.; Morizzi, J.; Nguyen, T.; Papastogiannidis, P.; Scheurer, C.; Shackleford, D.M.; Sriraghavan, K.; Stingelin, L.; Tang, Y.; Urwyler, H.; Wang, X.; White, K.L.; Wittlin, S.; Zhou, L.; Vennerstrom, J.L. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc. Natl. Acad. Sci. USA, 2011, 108(11), 4400-4405.
[] [PMID: 21300861]
Blackie, M.A.L.; Beagley, P.; Croft, S.L.; Kendrick, H.; Moss, J.R.; Chibale, K. Metallocene-based antimalarials: an exploration into the influence of the ferrocenyl moiety on in vitro antimalarial activity in chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. Bioorg. Med. Chem., 2007, 15(20), 6510-6516.
[] [PMID: 17693090]
Chibale, K.; Moss, J.R.; Blackie, M.; van Schalkwyk, D.; Smith, P.J. New amine and urea analogs of ferrochloroquine: synthesis, antimalarial activity in vitro and electrochemical studies. Tetrahedron Lett., 2000, 41(32), 6231-6235.
Dubar, F.; Egan, T.J.; Pradines, B.; Kuter, D.; Ncokazi, K.K.; Forge, D.; Paul, J.F.; Pierrot, C.; Kalamou, H.; Khalife, J.; Buisine, E.; Rogier, C.; Vezin, H.; Forfar, I.; Slomianny, C.; Trivelli, X.; Kapishnikov, S.; Leiserowitz, L.; Dive, D.; Biot, C. The antimalarial ferroquine: role of the metal and intramolecular hydrogen bond in activity and resistance. ACS Chem. Biol., 2011, 6(3), 275-287.
[] [PMID: 21162558]
Glans, L.; Ehnbom, A.; de Kock, C.; Martínez, A.; Estrada, J.; Smith, P.J.; Haukka, M.; Sánchez-Delgado, R.A.; Nordlander, E. Ruthenium(II) arene complexes with chelating chloroquine analogue ligands: synthesis, characterization and in vitro antimalarial activity. Dalton Trans., 2012, 41(9), 2764-2773.
[] [PMID: 22249579]
Hofheinz, W.; Masciadri, R. Antimalarial quinolin derivative. WO1997018193 1997.
Macedo, T.S.; Colina-Vegas, L.D.A.; Paixão, M.; Navarro, M.; Barreto, B.C.; Oliveira, P.C.M.; Macambira, S.G.; Machado, M.; Prudêncio, M.; D’Alessandro, S.; Basilico, N.; Moreira, D.R.M.; Batista, A.A.; Soares, M.B.P. Chloroquine-containing organoruthenium complexes are fast-acting multistage antimalarial agents. Parasitology, 2016, 143(12), 1543-1556.
[] [PMID: 27439976]
Fu, Y.; Tilley, L.; Kenny, S.; Klonis, N. Dual labeling with a far red probe permits analysis of growth and oxidative stress in P. falciparum-infected erythrocytes. Cytometry A, 2010, 77(3), 253-263.
[] [PMID: 20091670]
Prudêncio, M.; Mota, M.M.; Mendes, A.M. A toolbox to study liver stage malaria. Trends Parasitol., 2011, 27(12), 565-574.
[] [PMID: 22015112]
Rodrigues, T.; Prudêncio, M.; Moreira, R.; Mota, M.M.; Lopes, F. Targeting the liver stage of malaria parasites: a yet unmet goal. J. Med. Chem., 2012, 55(3), 995-1012.
[] [PMID: 22122518]
Kamiyama, T.; Matsubara, J. Application of a simple culture of Plasmodium berghei for assessment of antiparasitic activity. Int. J. Parasitol., 1992, 22(8), 1137-1142.
[] [PMID: 1487372]
Desjardins, R.E.; Canfield, C.J.; Haynes, J.D.; Chulay, J.D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob. Agents Chemother., 1979, 16(6), 710-718.
[] [PMID: 394674]
van Vianen, P.H.; Klayman, D.L.; Lin, A.J.; Lugt, C.B.; van Engen, A.L.; van der Kaay, H.J.; Mons, B. Plasmodium berghei: the antimalarial action of artemisinin and sodium artelinate in vivo and in vitro, studied by flow cytometry. Exp. Parasitol., 1990, 70(2), 115-123.
[] [PMID: 2404778]
Trager, W.; Jensen, J.B. Human malaria parasites in continuous culture. Science, 1976, 193(4254), 673-675.
[] [PMID: 781840]
Fujioka, H.; Nishiyama, Y.; Furukawa, H.; Kumada, N. In vitro and in vivo activities of atalaphillinine and related acridone alkaloids against rodent malaria. Antimicrob. Agents Chemother., 1989, 33(1), 6-9.
[] [PMID: 2653215]
Perez, H.A.; De la Rosa, M.; Apitz, R. In vivo activity of ajoene against rodent malaria. Antimicrob. Agents Chemother., 1994, 38(2), 337-339.
[] [PMID: 8192460]
Peters, W. The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity. Ann. Trop. Med. Parasitol., 1975, 69(2), 155-171.
[] [PMID: 1098584]
Martínez, A.; Rajapakse, C.S.K.; Naoulou, B.; Kopkalli, Y.; Davenport, L.; Sánchez-Delgado, R.A. The mechanism of antimalarial action of the ruthenium(II)-chloroquine complex [RuCl2(CQ)] (2). J. Biol. Inorg. Chem., 2008, 13(5), 703-712.
[] [PMID: 18305967]
Rajapakse, C.S.K.; Martínez, A.; Naoulou, B.; Jarzecki, A.A.; Suárez, L.; Deregnaucourt, C.; Sinou, V.; Schrével, J.; Musi, E.; Ambrosini, G.; Schwartz, G.K.; Sánchez-Delgado, R.A. Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine. Inorg. Chem., 2009, 48(3), 1122-1131.
[] [PMID: 19119867]
Navarro, M.; Vásquez, F.; Sánchez-Delgado, R.A.; Pérez, H.; Sinou, V.; Schrével, J. Toward a novel metal-based chemotherapy against tropical diseases. 7. Synthesis and in vitro antimalarial activity of new gold-chloroquine complexes. J. Med. Chem., 2004, 47(21), 5204-5209.
[] [PMID: 15456263]
Dive, D.; Biot, C. Ferrocene conjugates of chloroquine and other antimalarials: the development of ferroquine, a new antimalarial. ChemMedChem, 2008, 3(3), 383-391.
[] [PMID: 17806092]
Zamora, J.M.; Pearce, H.L.; Beck, W.T. Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Mol. Pharmacol., 1988, 33(4), 454-462.
[PMID: 3162758]
Sorensen, M.; Sehested, M.; Jensen, P.B. pH-dependent regulation of camptothecin-induced cytotoxicity and cleavable complex formation by the antimalarial agent chloroquine. Biochem. Pharmacol., 1997, 54(3), 373-380.
[] [PMID: 9278096]
Press, O.W.; DeSantes, K.; Anderson, S.K.; Geissler, F. Inhibition of catabolism of radiolabeled antibodies by tumor cells using lysosomotropic amines and carboxylic ionophores. Cancer Res., 1990, 50(4), 1243-1250.
[PMID: 2297772]
Ramakrishnan, S.; Houston, L.L. Inhibition of human acute lymphoblastic leukemia cells by immunotoxins: potentiation by chloroquine. Science, 1984, 223(4631), 58-61.
[] [PMID: 6318313]
Habtemariam, A.; Melchart, M.; Fernandez, R.; Parsons, S.; Oswald, I.D.H.; Parkin, A.; Fabbiani, F.P.A.; Davidson, J.E.; Dawson, A.; Aird, R.E.; Jodrell, D.I.; Sadler, P.J. Structure-activity relationships for cytotoxic ruthenium(II) arene complexes containing N,N-, N,O-, and O,O-chelating ligands. J. Med. Chem., 2006, 49(23), 6858-6868.
[] [PMID: 17154516]
Melchart, M.; Habtemariam, A.; Novakova, O.; Moggach, S.A.; Fabbiani, F.P.A.; Parsons, S.; Brabec, V.; Sadler, P.J. Bifunctional amine-tethered ruthenium(II) arene complexes form monofunctional adducts on DNA. Inorg. Chem., 2007, 46(21), 8950-8962.
[] [PMID: 17850143]
Strasberg Rieber, M.; Anzellotti, A.; Sánchez-Delgado, R.A.; Rieber, M. Tumor apoptosis induced by ruthenium(II)-ketoconazole is enhanced in nonsusceptible carcinoma by monoclonal antibody to EGF receptor. Int. J. Cancer, 2004, 112(3), 376-384.
[] [PMID: 15382061]
Martínez, A.; Rajapakse, C.S.K.; Jalloh, D.; Dautriche, C.; Sánchez-Delgado, R.A. The antimalarial activity of Ru-chloroquine complexes against resistant Plasmodium falciparum is related to lipophilicity, basicity, and heme aggregation inhibition ability near water/n-octanol interfaces. Eur. J. Biochem., 2009, 14(6), 863-871.
[] [PMID: 19343380]
Egan, T.J.; Chen, J.Y-J.; de Villiers, K.A.; Mabotha, T.E.; Naidoo, K.J.; Ncokazi, K.K.; Langford, S.J.; McNaughton, D.; Pandiancherri, S.; Wood, B.R. Haemozoin (β-haematin) biomineralization occurs by self-assembly near the lipid/water interface. FEBS Lett., 2006, 580(21), 5105-5110.
[] [PMID: 16956610]
Blackie, M.A.L.; Beagley, P.; Chibale, K.; Clarkson, C.; Moss, J.R.; Smith, P.J. Synthesis and antimalarial activity in vitro of new heterobimetallic complexes: Rh and Au derivatives of chloroquine and a series of ferrocenyl-4-amino-7-chloroquinolines. J. Organomet. Chem., 2003, 688(1-2), 144-152.
Glans, L.; Hu, W.; Jöst, C.; de Kock, C.; Smith, P.J.; Haukka, M.; Bruhn, H.; Schatzschneider, U.; Nordlander, E. Synthesis and biological activity of cymantrene and cyrhetrene 4-aminoquinoline conjugates against malaria, leishmaniasis, and trypanosomiasis. Dalton Trans., 2012, 41(21), 6443-6450.
[] [PMID: 22421887]
Makler, M.T.; Hinrichs, D.J. Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia. Am. J. Trop. Med. Hyg., 1993, 48(2), 205-210.
[] [PMID: 8447524]
De, D.; Krogstad, F.M.; Cogswell, F.B.; Krogstad, D.J. Aminoquinolines that circumvent resistance in Plasmodium falciparum in vitro. Am. J. Trop. Med. Hyg., 1996, 55(6), 579-583.
[] [PMID: 9025680]
Iwaniuk, D.P.; Whetmore, E.D.; Rosa, N.; Ekoue-Kovi, K.; Alumasa, J.; de Dios, A.C.; Roepe, P.D.; Wolf, C. Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain. Bioorg. Med. Chem., 2009, 17(18), 6560-6566.
[] [PMID: 19703776]
Arancibia, R.; Dubar, F.; Pradines, B.; Forfar, I.; Dive, D.; Klahn, A.H.; Biot, C. Synthesis and antimalarial activities of rhenium bioorganometallics based on the 4-aminoquinoline structure. Bioorg. Med. Chem., 2010, 18(22), 8085-8091.
[] [PMID: 20934349]
Friebolin, W.; Jannack, B.; Wenzel, N.; Furrer, J.; Oeser, T.; Sanchez, C.P.; Lanzer, M.; Yardley, V.; Becker, K.; Davioud-Charvet, E. Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum. J. Med. Chem., 2008, 51(5), 1260-1277.
[] [PMID: 18260613]
Ray, S.; Madrid, P.B.; Catz, P.; LeValley, S.E.; Furniss, M.J.; Rausch, L.L.; Guy, R.K.; DeRisi, J.L.; Iyer, L.V.; Green, C.E.; Mirsalis, J.C. Development of a new generation of 4-aminoquinoline antimalarial compounds using predictive pharmacokinetic and toxicology models. J. Med. Chem., 2010, 53(9), 3685-3695.
[] [PMID: 20361799]
Li, Y.; de Kock, C.; Smith, P.J.; Chibale, K.; Smith, G.S. Synthesis and evaluation of a carbosilane congener of ferroquine and its corresponding half-sandwich ruthenium and rhodium complexes for antiplasmodial and β-hematin inhibition activity. Organometallics, 2014, 33(17), 4345-4348.
de Hoog, P.; Pitié, M.; Amadei, G.; Gamez, P.; Meunier, B.; Kiss, R.; Reedijk, J. DNA cleavage and binding selectivity of a heterodinuclear Pt-Cu(3-Clip-Phen) complex. J. Biol. Inorg. Chem., 2008, 13(4), 575-586.
[] [PMID: 18270754]
Dong, X.; Wang, X.; Lin, M.; Sun, H.; Yang, X.; Guo, Z. Promotive effect of the platinum moiety on the DNA cleavage activity of copper-based artificial nucleases. Inorg. Chem., 2010, 49(5), 2541-2549.
[] [PMID: 20121144]
Donzello, M.P.; Viola, E.; Ercolani, C.; Fu, Z.; Futur, D.; Kadish, K.M. Tetra-2,3-pyrazinoporphyrazines with externally appended pyridine rings. 12. New heteropentanuclear complexes carrying four exocyclic cis-platin-like functionalities as potential bimodal (PDT/cis-platin) anticancer agents. Inorg. Chem., 2012, 51(22), 12548-12559.
[] [PMID: 23121685]
González-Pantoja, J.F.; Stern, M.; Jarzecki, A.A.; Royo, E.; Robles-Escajeda, E.; Varela-Ramírez, A.; Aguilera, R.J.; Contel, M. Titanocene-phosphine derivatives as precursors to cytotoxic heterometallic TiAu2 and TiM (M = Pd, Pt) compounds. Studies of their interactions with DNA. Inorg. Chem., 2011, 50(21), 11099-11110.
[] [PMID: 21958150]
Glans, L.; Taylor, D.; de Kock, C.; Smith, P.J.; Haukka, M.; Moss, J.R.; Nordlander, E. Synthesis, characterization and antimalarial activity of new chromium arene-quinoline half sandwich complexes. J. Inorg. Biochem., 2011, 105(7), 985-990.
[] [PMID: 21565148]
Blackie, M.A.; Yardley, V.; Chibale, K. Synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo. Bioorg. Med. Chem. Lett., 2010, 20(3), 1078-1080.
[] [PMID: 20034790]
Kumar, K.; Schniper, S.; González-Sarrías, A.; Holder, A.A.; Sanders, N.; Sullivan, D.; Jarrett, W.L.; Davis, K.; Bai, F.; Seeram, N.P.; Kumar, V. Highly potent anti-proliferative effects of a gallium(III) complex with 7-chloroquinoline thiosemicarbazone as a ligand: synthesis, cytotoxic and antimalarial evaluation. Eur. J. Med. Chem., 2014, 86, 81-86.
[] [PMID: 25147149]
Johnson, J.D.; Dennull, R.A.; Gerena, L.; Lopez-Sanchez, M.; Roncal, N.E.; Waters, N.C. Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening. Antimicrob. Agents Chemother., 2007, 51(6), 1926-1933.
[] [PMID: 17371812]
Wasi, N.; Singh, H.B. Synthesis of metal complexes of antimalarial drugs and in vitro evaluation of their activity against P. falciparum. Inorg. Chim. Acta, 1987, 135, 133-137.
Khan, M.O.F.; Levi, M.S.; Tekwani, B.L.; Khan, S.I.; Kimura, E.; Borne, R.F. Synthesis and antimalarial activities of cyclen 4-aminoquinoline analogs. Antimicrob. Agents Chemother., 2009, 53(4), 1320-1324.
[] [PMID: 19171802]

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