Structure-activity relationships of Toxoplasma gondii cytochrome bc₁ inhibitors

References

• Dubey JP. The history of Toxoplasma gondii- the first 100 years. J Eukaryot Microbiol. 2008;55(6):467–475.
   PubMed Web of Science ®Google Scholar
• Arruda S, Vieira BR, Garcia DM, et al. Clinical manifestations and visual outcomes associated with ocular toxoplasmosis in a Brazilian population. Sci Rep. 2021;11(1):3137.
   PubMed Web of Science ®Google Scholar
• Dunay IR, Gajurel K, and Dhakal R, et al. Treatment of Toxoplasmosis: historical perspective, animal models, and current clinical practice. Clin Microbiol Rev. 2018;31(4).
   PubMed Web of Science ®Google Scholar
• Yan J, Huang B, Liu G, et al. Meta-analysis of prevention and treatment of toxoplasmic encephalitis in HIV-infected patients. Acta Trop. 2013;127(3):236–244.
   PubMed Web of Science ®Google Scholar
• Lindsay DS, Toivio-Kinnucan MA, and Blagburn BL. Decoquinate induces tissue cyst formation by the RH strain of Toxoplasma gondii. Vet Parasitol. 1998;77(2–3):75–81.
   PubMed Web of Science ®Google Scholar
• Doggett JS, Nilsen A, Forquer I, et al. Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis. Proc Natl Acad Sci. 2012;109(39):15936–15941.
   PubMed Web of Science ®Google Scholar
• Taylor MA, Bartram DJ. The history of decoquinate in the control of coccidial infections in ruminants. J Vet Pharmacol Ther. 2012;35(5):417–427.
   PubMed Web of Science ®Google Scholar
• Anghel N, Balmer V, and Müller J, et al. Endochin-like quinolones exhibit promising efficacy against Neospora caninum in vitro and in experimentally infected pregnant mice. Front Vet Sci. 2018;5:1473–15.
   Web of Science ®Google Scholar
• Eberhard N, Balmer V, and Müller J, et al. Activities of endochin-like quinolones against in vitro cultured Besnoitia besnoiti tachyzoites. Front Vet Sci. 2020;7:96.
   PubMed Web of Science ®Google Scholar
• Silva MG, Bastos RG, and Doggett JS, et al. Endochin-like quinolone-300 and ELQ-316 inhibit Babesia bovis, B. bigemina, B. caballi and Theileria equi. Parasite Vector. 2020;13(1):606.
   PubMed Web of Science ®Google Scholar
• Tsaousis AD, and Keithly JS. The mitochondrion-related organelles of cryptosporidium species. Cham, Switzerland: Springer International Publishing; 2019. p. 243–266.
   Google Scholar
• Painter HJ, Morrisey JM, and Mather MW, et al. Atypical molecular basis for drug resistance to mitochondrial function inhibitors in Plasmodium falciparum. Antimicrob Agents Ch. 2021;65(3).
   PubMed Web of Science ®Google Scholar
• Ganesan SM, Morrisey JM, and Ke H, et al. Yeast dihydroorotate dehydrogenase as a new selectable marker for Plasmodium falciparum transfection. Molecular and Biochemical Parasitology. 2011;177(1):29–34.
   PubMed Web of Science ®Google Scholar
• Goodman CD, Siregar JE, Mollard V, et al. Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes. Science. 2016;352(6283):349–353.
   PubMed Web of Science ®Google Scholar
• Chiu JE, Renard I, and George S, et al. Cytochrome b drug resistance mutation decreases babesia fitness in the tick stages but not the mammalian erythrocytic cycle. J Infect Dis. 2021;225(1):135–145.
   Web of Science ®Google Scholar
• Fox BA, and Bzik DJ. De novo pyrimidine biosynthesis is required for virulence of Toxoplasma gondii. Nature. 2002;415(6874):926–929.
   PubMed Web of Science ®Google Scholar
• Vercesi AE, Rodrigues CO, and Uyemura SA, et al. Respiration and oxidative phosphorylation in the apicomplexan parasite Toxoplasma gondii. J Biol Chem. 1998;273(47):31040–31047.
   PubMed Web of Science ®Google Scholar
• Wendel W. The influence of napthoquinones upon the respiratory and carbohydrate metabolism of malarial parasites. Fed Proc. 1946;5:406.
   PubMedGoogle Scholar
• Hudson AT, Dickins M, Ginger CD, et al. 566C80: a potent broad spectrum anti-infective agent with activity against malaria and opportunistic infections in AIDS patients. Drug Exp Clin Res. 1991;17.427–435.
   PubMedGoogle Scholar
• Araujo FG, Huskinson J, and Remington JS. Remarkable in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother. 1991;35(2):293–299.
   PubMed Web of Science ®Google Scholar
• Gutteridge W. 566C80, an antimalarial hydroxynaphthoquinone with broad spectrum: experimental activity against opportunistic parasitic infections of AIDS patients. J Protozool. 1991;6:141S–143S.
   Google Scholar
• Kovacs JA, Program TN-CCIA. Efficacy of atovaquone in treatment of toxoplasmosis in patients with AIDS. Lancet. 1992;340(8820):637–638.
   PubMed Web of Science ®Google Scholar
• Khan AA, Nasr M, and Araujo FG. Two 2-hydroxy-3-alkyl-1,4-naphthoquinones with in vitro and in vivo activities against Toxoplasma gondii. Antimicrob Agents Chemother. 1998;42(9):2284–2289.
   PubMed Web of Science ®Google Scholar
• Ferreira RA, Oliveira AB, and Gualberto SA, et al. Activity of natural and synthetic naphthoquinones against Toxoplasma gondii, in vitro and in murine models of infection. Parasite. 2002;9(3):261–269.
   PubMedGoogle Scholar
• Ferreira RA, Oliveira AB, and Ribeiro MFB, et al. Toxoplasma gondii: in vitro and in vivo activities of the hydroxynaphthoquinone 2-hydroxy-3-(1′-propen-3-phenyl)-1,4-naphthoquinone alone or combined with sulfadiazine. Exp Parasitol. 2006;113(2):125–129.
   PubMed Web of Science ®Google Scholar
• Ferreira RA, de Oliveira AB, and Gualberto SA, et al. New naphthoquinones and an alkaloid with in vitro activity against Toxoplasma gondii RH and EGS strains. Exp Parasitol. 2012;132(4):450–457.
   PubMed Web of Science ®Google Scholar
• Fry M, Pudney M. Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4’-chlorophenyl) cyclohexyl]-3- hydroxy-1,4-naphthoquinone (566C80). Biochem Pharmacol. 1992;43(7):1545–1553.
   PubMed Web of Science ®Google Scholar
• Korsinczky M, Chen N, and Kotecka B, et al. Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother. 2000;44(8):2100–2108.
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Lange BB, and Merbitz-Zahradnik T, et al. Molecular basis for atovaquone binding to the cytochrome bc1 complex. J Biol Chem. 2003;278(33):31312–31318.
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Ha KH, and Merritt AK, et al. Cytochrome b mutations that modify the ubiquinol-binding pocket of the cytochrome bc1 complex and confer anti-malarial drug resistance in Saccharomyces cerevisiae. J Biol Chem. 2005;280(17):17142–17148.
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Meshnick SR, Trumpower BL. Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi. Trends Parasitol. 2007;23(10):494–501.
   PubMed Web of Science ®Google Scholar
• Fisher N, and Meunier B. Molecular basis of resistance to cytochrome bc1 inhibitors. Fems Yeast Res. 2008;8(2):183–192.
   PubMed Web of Science ®Google Scholar
• Birth D, Kao W-C, and Hunte C. Structural analysis of atovaquone-inhibited cytochrome bc1 complex reveals the molecular basis of antimalarial drug action. Nat Commun. 2014;5(1):4029.
   PubMedGoogle Scholar
• Biagini GA, Fisher N, and Berry N, et al. Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complex. Mol Pharmacol. 2008;73(5):1347–1355.
   PubMed Web of Science ®Google Scholar
• Nilsen A, LaCrue AN, White KL, et al. Quinolone-3-diarylethers: a new class of antimalarial drug. Sci Transl Med. 2013;5(177):177.
   Web of Science ®Google Scholar
• Abbass A, Khalid S, and Farooq U, et al. If DILI is suspected, don’t dally. Digest Dis Sci. 2021;66(1):52–55.
   PubMed Web of Science ®Google Scholar
• Taylor WRJ, White NJ. Antimalarial drug toxicity. Drug Saf. 2004;27(1):25–61.
   PubMed Web of Science ®Google Scholar
• Falloon J, Sargent S, Piscitelli SC, et al. Atovaquone suspension in HIV‐infected volunteers: pharmacokinetics, pharmacodynamics, and TMP‐SMX interaction study. Pharmacother J Hum Pharmacol Drug Ther. 1999;19(9):1050–1056.
   Google Scholar
• Fiorillo M, Lamb R, Tanowitz HB, et al. Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells. Oncotarget. 2016;7(23):34084–34099.
   PubMedGoogle Scholar
• Guo Y, Hu B, and Fu B, et al. Atovaquone at clinically relevant concentration overcomes chemoresistance in ovarian cancer via inhibiting mitochondrial respiration. Pathology - Res Pract. 2021;224:153529. DOI: 10.1016/j.prp.2021.153529
   PubMed Web of Science ®Google Scholar
• Wilde L, Roche M, Domingo-Vidal M, et al. Metabolic coupling and the reverse Warburg effect in cancer: implications for novel biomarker and anticancer agent development. Semin Oncol. 2017;44(3):198–203.
   PubMed Web of Science ®Google Scholar
• Kessl JJ, Hill P, and Lange BB, et al. Molecular basis for atovaquone resistance in Pneumocystis jirovecii modeled in the cytochrome bc1 complex of Saccharomyces cerevisiae. J Biol Chem. 2004;279(4):2817–2824.
   PubMed Web of Science ®Google Scholar
• Fisher N, Majid RA, and Antoine T, et al. Cytochrome b mutation Y268S conferring atovaquone resistance phenotype in malaria parasite results in reduced parasite bc1catalytic turnover and protein expression. J Biol Chem. 2012;287(13):9731–9741.
   PubMed Web of Science ®Google Scholar
• Vallières C, Fisher N, and Meunier B. Reconstructing the Qo site of Plasmodium falciparum bc1 complex in the yeast enzyme. Plos One. 2013;8(8):e71726.
   PubMed Web of Science ®Google Scholar
• Ricketts AP, and Pfefferkorn ER. Toxoplasma gondii: susceptibility and development of resistance to anticoccidial drugs in vitro. Antimicrob Agents Chemother. 1993;37(11):2358–2363.
   PubMed Web of Science ®Google Scholar
• Buxton D, Brebner J, Wright S, et al. Decoquinate and the control of experimental ovine toxoplasmosis. Vet Rec. 1996;138(18):434–436.
   PubMed Web of Science ®Google Scholar
• EFSA Panel on Additives, Products or Substances used in Animal Feed (EFSA FEEDAP Panel), Bampidis V, Azimonti G, and Bastos, M, et al. Safety and efficacy of Deccox® (decoquinate) for chickens for fattening. EFSA J. 2019;17(1):e05541.
   PubMed Web of Science ®Google Scholar
• Beteck RM, Seldon R, and Coertzen D, et al. Accessible and distinct decoquinate derivatives active against Mycobacterium tuberculosis and apicomplexan parasites. Commun Chem. 2018;1(1):62.
   Google Scholar
• Ramseier J, Imhof D, and Anghel N, et al. Assessment of the activity of decoquinate and its quinoline-O-carbamate derivatives against Toxoplasma gondii in vitro and in pregnant mice infected with T. gondii oocysts. Molecules. 2021;26(21):6393.
   PubMed Web of Science ®Google Scholar
• Wang CC. Studies of the mitochondria from Eimeria tenella and inhibition of the electron transport by quinolone coccidiostats. Biochim Biophys Acta Bioenerg. 1975;396(2):210–219.
   Google Scholar
• Wang CC. Inhibition of the respiration of Eimeria tenella by quinolone coccidiostats. Biochem Pharmacol. 1976;25(3):343–349.
   PubMed Web of Science ®Google Scholar
• Fry M, and Williams RB. Effects of decoquinate and clopidol on electron transport in mitochondria of Eimeria tenella (Apicomplexa: coccidia). Biochem Pharmacol. 1984;33(2):229–240.
   PubMed Web of Science ®Google Scholar
• Pfefferkorn ER, Borotz SE, and Nothnagel RF. Mutants of Toxoplasma gondii resistant to atovaquone (566C80) or decoquinate. J Parasitol. 1993;79(4):559–564.
   PubMed Web of Science ®Google Scholar
• McFadden DC, and Boothroyd JC. Cytochrome b mutation identified in a decoquinate-resistant mutant of Toxoplasma gondii. J Eukaryot Microbiol. 1999;46(5):81S–82S.
   PubMed Web of Science ®Google Scholar
• Eschemann A, Galkin A, and Oettmeier W, et al. HDQ (1-Hydroxy-2-dodecyl-4(1H)quinolone), a high affinity inhibitor for mitochondrial alternative NADH dehydrogenase: evidence for a ping-pong mechanism. J Biol Chem. 2005;280(5):3138–3142.
   PubMed Web of Science ®Google Scholar
• Saleh A, Friesen J, and Baumeister S, et al. Growth Inhibition of Toxoplasma gondii and Plasmodium falciparum by nanomolar concentrations of 1-hydroxy-2-dodecyl-4(1H)quinolone, a high-affinity inhibitor of alternative (Type II) NADH dehydrogenases. Antimicrob Agents Chemother. 2007;51(4):1217–1222.
   PubMed Web of Science ®Google Scholar
• Bajohr LL, Ma L, and Platte C, et al. In vitro and in vivo activities of 1-hydroxy-2-alkyl-4(1H)quinolone derivatives against Toxoplasma gondii. Antimicrob Agents Chemother. 2010;54(1):517–521.
   PubMed Web of Science ®Google Scholar
• Salzer W, Timmler H, Andersag H. Über einen neuen, gegen Vogelmalaria wirksamen Verbindungstypus. Chem Ber. 1948;81(1):12–19.
   Google Scholar
• Gingrich WD, Darrow EM. The effect of endochin on experimental toxoplasmosis. Am J Tropical Medicine Hyg. 1951;s1-31(1):12–17.
   Web of Science ®Google Scholar
• Winter RW, Kelly JX, Smilkstein MJ, et al. Antimalarial quinolones: synthesis, potency, and mechanistic studies. Exp Parasitol. 2008;118(4):487–497.
   PubMed Web of Science ®Google Scholar
• McConnell EV, Bruzual I, and Pou S, et al., Targeted structure–activity analysis of endochin-like quinolones reveals potent Qi and Qo site inhibitors of Toxoplasma gondii and Plasmodium falciparum cytochrome bc1 and identifies ELQ-400 as a remarkably effective compound against acute experimental toxoplasmosis. ACS Infect Dis. 2018;4(11):1574–1584.
   PubMed Web of Science ®Google Scholar
• Hegewald J, Gross U, and Bohne W. Identification of dihydroorotate dehydrogenase as a relevant drug target for 1-hydroxyquinolones in Toxoplasma gondii. Mol Biochem Parasit. 2013;190(1):6–15.
   PubMed Web of Science ®Google Scholar
• Vallières C, Fisher N, and Antoine T, et al. HDQ, a potent inhibitor of Plasmodium falciparum proliferation, binds to the quinone reduction site of the cytochrome bc1 complex. Antimicrob Agents Chemother. 2012;56(7):3739–3747.
   PubMed Web of Science ®Google Scholar
• Markley LD, Heertum JCV, and Doorenbos HE. Antimalarial activity of clopidol, 3,5-dichloro-2,6-dimethyl-4-pyridinol, and its esters, carbonates, and sulfonates. J Med Chem. 1972;15(11):1188–1189.
   PubMed Web of Science ®Google Scholar
• Capper MJ, O’Neill PM, and Fisher N, et al., Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1. Proc Natl Acad Sci. 2015;112(3):755–760.
   PubMed Web of Science ®Google Scholar
• Winter R, Kelly JX, Smilkstein MJ, et al. Optimization of endochin-like quinolones for antimalarial activity. Exp Parasitol. 2011;127(2):545–551.
   PubMed Web of Science ®Google Scholar
• Yeates CL, Batchelor JF, Capon EC, et al. Synthesis and structure–activity relationships of 4-pyridones as potential antimalarials. J Med Chem. 2008;51(9):2845–2852.
   PubMed Web of Science ®Google Scholar
• Nilsen A, Forquer IP, Riscoe MK, et al. Inhibition of cytochrome bc1 as a strategy for single-dose, multi-stage antimalarial therapy. Am J Tropical Medicine Hyg. 2015;92(6):1195–1201.
   PubMed Web of Science ®Google Scholar
• Nilsen A, Miley GP, and Forquer IP, et al. Discovery, Synthesis, and Optimization of Antimalarial 4(1H)-Quinolone-3-Diarylethers. J Med Chem. 2014;57(9):3818–3834.
   PubMed Web of Science ®Google Scholar
• Stickles AM, de Almeida MJ, and Morrisey JM, et al. Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum. Antimicrob Agents Chemother. 2015;59(4):1977–1982.
   PubMed Web of Science ®Google Scholar
• Lawres LA, Garg A, Kumar V, et al. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone. J Exp Medicine. 2016;213(7):1307–1318.
   PubMed Web of Science ®Google Scholar
• Frueh L, Li Y, Mather MW, et al. Alkoxycarbonate ester prodrugs of preclinical drug candidate ELQ-300 for prophylaxis and treatment of malaria. ACS Infect Dis. 2017;3(10):728–735.
   PubMed Web of Science ®Google Scholar
• Doggett JS, Schultz T, and Miller AJ, et al. Orally bioavailable endochin-like quinolone carbonate ester prodrug reduces Toxoplasma gondii brain cysts. Antimicrob Agents Chemother. 2020;65(9): e00535–20.
   Google Scholar
• Pidathala C, Amewu R, and Pacorel B, et al. Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:quinone oxidoreductase (PfNDH2). J Med Chem. 2012;55(5):1831–1843.
   PubMed Web of Science ®Google Scholar
• Yang Y, Yu Y, and Li X, et al. Target elucidation by cocrystal structures of NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) with small molecule to eliminate drug-resistant malaria. J Med Chem. 2017;60(5):1994–2005.
   PubMed Web of Science ®Google Scholar
• Hong WD, Leung SC, and Amporndanai K, et al. Potent antimalarial 2-pyrazolyl quinolone bc1 (Qi) inhibitors with improved drug-like properties. ACS Med Chem Lett. 2018;9(12):1205–1210.
   PubMed Web of Science ®Google Scholar
• Lane KD, Mu J, and Lu J, et al. Selection of Plasmodium falciparum cytochrome b mutants by putative PfNDH2 inhibitors. Proc Natl Acad Sci. 2018;115:6285–6290.
   PubMed Web of Science ®Google Scholar
• Ke H, Ganesan SM, and Dass S, et al. Mitochondrial type II NADH dehydrogenase of Plasmodium falciparum (PfNDH2) is dispensable in the asexual blood stages. Plos One. 2019;14:e0214023.
   PubMed Web of Science ®Google Scholar
• Sidik SM, Huet D, and Ganesan SM, et al. A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell. 2016;166(6):1423–1435.
   PubMed Web of Science ®Google Scholar
• Alday PH, Bruzual I, and Nilsen A, et al. Genetic evidence for cytochrome b Qi site inhibition by 4(1H)-quinolone-3-diarylethers and antimycin in Toxoplasma gondii. Antimicrob Agents Chemother. 2017;61(2):e01866–16.
   PubMed Web of Science ®Google Scholar
• Potter VR, Reif AE. Inhibition of an electron transport component by antimycin A. J Biol Chem. 1952;194(1):287–297.
   PubMed Web of Science ®Google Scholar
• McPhillie M, Zhou Y, Bissati KE, et al. New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. Sci Rep. 2016;6(1):1–23.
   PubMedGoogle Scholar
• McPhillie MJ, Zhou Y, Hickman MR, et al. Potent tetrahydroquinolone eliminates apicomplexan parasites. Front Cell Infect Microbiol. 2020;10:203.
   PubMed Web of Science ®Google Scholar
• Stephen JML, Tonkin IM, Walker J. Antimalarial activity in tetrahydro-acridones and related substances. Nature. 1945;156(3969):629–629.
   PubMedGoogle Scholar
• Winter RW, Kelly JX, Smilkstein MJ, et al. Evaluation and lead optimization of anti-malarial acridones. Exp Parasitol. 2006;114(1):47–56.
   PubMed Web of Science ®Google Scholar
• Kelly JX, Smilkstein MJ, Brun R, et al. Discovery of dual function acridones as a new antimalarial chemotype. Nature. 2009;459(7244):270–273.
   PubMed Web of Science ®Google Scholar
• Dodean RA, Kancharla P, Li Y, et al. Discovery and structural optimization of acridones as broad-spectrum antimalarials. J Med Chem. 2019;62(7):3475–3502.
   PubMed Web of Science ®Google Scholar
• Kancharla P, Dodean RA, Li Y, et al. Lead optimization of second-generation acridones as broad-spectrum antimalarials. J Med Chem. 2020;63(11):6179–6202.
   PubMed Web of Science ®Google Scholar
• Alday PH, McConnell EV, and Zarella JMB, et al. Acridones are highly potent inhibitors of Toxoplasma gondii tachyzoites. ACS Infect Dis. 2021;7(7):1877–1884.
   PubMed Web of Science ®Google Scholar
• Bueno JM, Herreros E, Angulo-Barturen I, et al. Exploration of 4(1H)-pyridones as a novel family of potent antimalarial inhibitors of the plasmodial cytochrome bc1. Future Med Chem. 2012;4(18):2311–2323.
   PubMed Web of Science ®Google Scholar
• Stickles AM, Smilkstein MJ, and Morrisey JM, et al. Atovaquone and ELQ-300 combination therapy as a novel dual-site cytochrome bc1 inhibition strategy for malaria. Antimicrob Agents Chemother. 2016;60(8):4853–4859.
   PubMed Web of Science ®Google Scholar
• Smilkstein MJ, Pou S, Krollenbrock A, et al. ELQ-331 as a prototype for extremely durable chemoprotection against malaria. Malaria J. 2019;18(1):291.
   PubMed Web of Science ®Google Scholar
• Wenz T, Hellwig P, MacMillan F, et al. Probing the role of E272 in quinol oxidation of mitochondrial complex III. Biochemistry. 2006;45(30):9042–9052.
   PubMed Web of Science ®Google Scholar
• Song Z, Iorga BI, and Mounkoro P, et al. The antimalarial compound ELQ−400 is an unusual inhibitor of the bc1 complex, targeting both Qo and Qi sites. FEBS Lett. 2018;592(8):1346–1356.
   PubMed Web of Science ®Google Scholar
• Martynowicz J, Doggett JS, and Sullivan WJ. Efficacy of guanabenz combination therapy against chronic toxoplasmosis across multiple mouse strains. Antimicrob Agents Chemother. 2020;64(9):e00539–20.
   PubMed Web of Science ®Google Scholar
• Doggett J. Simultaneous Inhibition of both cytochrome b substrate binding sites is synergistic against experimental toxoplasmosis. XV Int Congre Toxoplasma Toxoplasmosis. 2019
   Google Scholar
• Tomavo S, and Boothroyd JC. Interconnection between organellar functions, development and drug resistance in the protozoan parasite, Toxoplasma gondii. Int J Parasitol. 1995;25(11):1293–1299.
   PubMed Web of Science ®Google Scholar
• Christiansen C, Maus D, and Hoppenz E, et al. In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization. Nat Commun. 2022;13(1):1168.
   PubMed Web of Science ®Google Scholar
• Muller FL, Roberts AG, Bowman MK, et al. Architecture of the Qo Site of the Cytochrome bc1 Complex Probed by Superoxide Production. Biochemistry. 2003;42:6493–6499. DOI:10.1021/bi0342160.
   PubMed Web of Science ®Google Scholar
• Chirgwin K, Hafner R, and Leport C, et al. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 study. AIDS clinical trials group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. Clin Infect Dis. 2002;34(9):1243–1250.
   PubMed Web of Science ®Google Scholar
• Bakshi RP, Tatham LM, Savage AC, et al. Long-acting injectable atovaquone nanomedicines for malaria prophylaxis. Nat Commun. 2018;9(1):315.
   PubMedGoogle Scholar