Antitrypanosomal treatment with benznidazole is superior to posaconazole regimens in mouse models of Chagas disease

Antimicrobial Agents and Chemotherapy

Volumn 59, Issue 10, 2015, Pages 6385-6394

  Khare, Shilpi ^a   Liu, Xianzhong ^a   Stinson, Monique ^a   Rivera, Ianne ^a   Groessl, Todd ^a   Tuntland, Tove ^a   Yeh, Vince ^a   Wen, Ben ^a   Molteni, Valentina ^a   Glynne, Richard ^a   Supek, Frantisek ^a  

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZNIDAZOLE; CYCLOPHOSPHAMIDE; POSACONAZOLE; ANTITRYPANOSOMAL AGENT; NITROIMIDAZOLE DERIVATIVE; STEROL 14ALPHA DEMETHYLASE; STEROL 14ALPHA DEMETHYLASE INHIBITOR; TRIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMICROBIAL THERAPY; ANTIPROTOZOAL ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CHAGAS DISEASE; CONTROLLED STUDY; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE REGIMEN; DRUG ELIMINATION; DRUG HALF LIFE; ELIMINATION RATE CONSTANT; IMMUNOSUPPRESSIVE TREATMENT; LIMIT OF DETECTION; LOW DRUG DOSE; MAXIMUM PLASMA CONCENTRATION; MOUSE; MOUSE MODEL; NONHUMAN; OUTCOME ASSESSMENT; PARASITE LOAD; PARASITEMIA; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; SINGLE DRUG DOSE; TREATMENT DURATION; TRYPANOSOMA CRUZI; TRYPOMASTIGOTE; VOLUME OF DISTRIBUTION AT STEADY-STATE; 3T3 CELL LINE; ANIMAL; DISEASE MODEL; DRUG ADMINISTRATION; DRUG EFFECTS; ENZYMOLOGY; HEART; HUMAN; IMMUNOLOGY; METABOLISM; ORAL DRUG ADMINISTRATION; PARASITOLOGY; PATHOGENICITY; PHASE 2 CLINICAL TRIAL (TOPIC); PHYSIOLOGY; RECURRENT DISEASE;

14-ALPHA DEMETHYLASE INHIBITORS; ADMINISTRATION, ORAL; ANIMALS; CHAGAS DISEASE; CLINICAL TRIALS, PHASE II AS TOPIC; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; HEART; HUMANS; IMMUNOSUPPRESSION; MICE; NIH 3T3 CELLS; NITROIMIDAZOLES; PARASITEMIA; RECURRENCE; STEROL 14-DEMETHYLASE; TRIAZOLES; TRYPANOCIDAL AGENTS; TRYPANOSOMA CRUZI;

EID: 84942889762     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00689-15     Document Type: Article

References (38)

1. WHO. 2015. Chagas disease (American trypanosomiasis). Fact sheet no. 340. World Health Organization, Geneva, Switzerland. http://www.who.int/mediacentre/factsheets/fs340/en/.
2. Bern C, Kjos S, Yabsley MJ, Montgomery SP. 2011. Trypanosoma cruzi and Chagas' disease in the United States. Clin Microbiol Rev 24:655-681. http://dx.doi.org/10.1128/CMR.00005-11.
3. Bahia-Oliveira LM, Gomes JA, Cancado JR, Ferrari TC, Lemos EM, Luz ZM, Moreira MC, Gazzinelli G, Correa-Oliveira R. 2000. Immunological and clinical evaluation of chagasic patients subjected to chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years ago. J Infect Dis 182:634-638. http://dx.doi.org/10.1086/315743.
4. Cancado JR. 2002. Long term evaluation of etiological treatment of Chagas disease with benznidazole. Rev Inst Med Trop Sao Paulo 44:29-37. http://dx.doi.org/10.1590/S0036-46652002000100006.
5. Viotti R, Vigliano C, Lococo B, Alvarez MG, Petti M, Bertocchi G, Armenti A. 2009. Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities. Expert Rev Anti Infect Ther 7:157-163. http://dx.doi.org/10.1586/14787210.7.2.157.
6. Urbina JA. 2010. Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Trop 115:55-68. http://dx.doi.org/10.1016/j.actatropica.2009.10.023.
7. Buckner FS, Urbina JA. 2012. Recent developments in sterol 14-demethylase inhibitors for Chagas disease. Int J Parasitol Drugs Drug Resist 2:236-242. http://dx.doi.org/10.1016/j.ijpddr.2011.12.002.
8. Diniz Lde F, Urbina JA, de Andrade IM, Mazzeti AL, Martins TA, Caldas IS, Talvani A, Ribeiro I, Bahia MT. 2013. Benznidazole and posaconazole in experimental Chagas disease: positive interaction in concomitant and sequential treatments. PLoS Negl Trop Dis 7:e2367. http://dx.doi.org/10.1371/journal.pntd.0002367.
9. Bustamante JM, Craft JM, Crowe BD, Ketchie SA, Tarleton RL. 2014. New, combined, and reduced dosing treatment protocols cure Trypanosoma cruzi infection in mice. J Infect Dis 209:150-162. http://dx.doi.org/10.1093/infdis/jit420.
10. Chatelain E. 2015. Chagas disease drug discovery: toward a new era. J Biomol Screen. 20:22-35. http://dx.doi.org/10.1177/1087057114550585.
11. Urbina JA. 2015. Recent clinical trials for the etiological treatment of chronic Chagas disease: advances, challenges and perspectives. J Eukaryot Microbiol 62:149-156. http://dx.doi.org/10.1111/jeu.12184.
12. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, Guertin DA, Chang JH, Lindquist RA, Moffat J, Golland P, Sabatini DM. 2006. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7:R100. http://dx.doi.org/10.1186/gb-2006-7-10-r100.
13. Bustamante JM, Bixby LM, Tarleton RL. 2008. Drug-induced cure drives conversion to a stable and protective CD8+ T central memory response in chronic Chagas disease. Nat Med 14:542-550. http://dx.doi.org/10.1038/nm1744.
14. Caldas S, Santos FM, de Lana M, Diniz LF, Machado-Coelho GL, Veloso VM, Bahia MT. 2008. Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole. Exp Parasitol 118:315-323. http://dx.doi.org/10.1016/j.exppara.2007.08.016.
15. Richle RW, Raaflaub J. 1980. Difference of effective antitrypanosomal dosages of benznidazole in mice and man. Chemotherapeutic and pharmacokinetic results. Acta Trop 37:257-261.
16. Urbina JA, Payares G, Contreras LM, Liendo A, Sanoja C, Molina J, Piras M, Piras R, Perez N, Wincker P, Loebenberg D. 1998. Antiproliferative effects and mechanism of action of SCH 56592 against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies. Antimicrob Agents Chemother 42:1771-1777.
17. Olivieri BP, Molina JT, de Castro SL, Pereira MC, Calvet CM, Urbina JA, Araujo-Jorge TC. 2010. A comparative study of posaconazole and benznidazole in the prevention of heart damage and promotion of trypanocidal immune response in a murine model of Chagas disease. Int J Antimicrob Agents 36:79-83. http://dx.doi.org/10.1016/j.ijantimicag.2010.03.006.
18. Molina I, Gomez i Prat J, Salvador F, Trevino B, Sulleiro E, Serre N, Pou D, Roure S, Cabezos J, Valerio L, Blanco-Grau A, Sanchez-Montalva A, Vidal X, Pahissa A. 2014. Randomized trial of posaconazole and benznidazole for chronic Chagas' disease. N Engl J Med 370:1899-1908. http://dx.doi.org/10.1056/NEJMoa1313122.
19. Krishna G, Moton A, Ma L, Medlock MM, McLeod J. 2009. Pharmacokinetics and absorption of posaconazole oral suspension under various gastric conditions in healthy volunteers. Antimicrob Agents Chemother 53:958-966. http://dx.doi.org/10.1128/AAC.01034-08.
20. Andriani G, Amata E, Beatty J, Clements Z, Coffey BJ, Courtemanche G, Devine W, Erath J, Juda CE, Wawrzak Z, Wood JT, Lepesheva GI, Rodriguez A, Pollastri MP. 2013. Antitrypanosomal lead discovery: identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth. J Med Chem 56:2556-2567. http://dx.doi.org/10.1021/jm400012e.
21. Calvet CM, Vieira DF, Choi JY, Kellar D, Cameron MD, Siqueira-Neto JL, Gut J, Johnston JB, Lin L, Khan S, McKerrow JH, Roush WR, Podust LM. 2014. 4-Aminopyridyl-based CYP51 inhibitors as anti-Trypanosoma cruzi drug leads with improved pharmacokinetic profile and in vivo potency. J Med Chem 57:6989-7005. http://dx.doi.org/10.1021/jm500448u.
22. Choi JY, Calvet CM, Gunatilleke SS, Ruiz C, Cameron MD, McKerrow JH, Podust LM, Roush WR. 2013. Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-Chagas agents. J Med Chem 56:7651-7668. http://dx.doi.org/10.1021/jm401067s.
23. Friggeri L, Hargrove TY, Rachakonda G, Williams AD, Wawrzak Z, Di Santo R, De Vita D, Waterman MR, Tortorella S, Villalta F, Lepesheva GI. 2014. Structural basis for rational design of inhibitors targeting Trypanosoma cruzi sterol 14alpha-demethylase: two regions of the enzyme molecule potentiate its inhibition. J Med Chem 57:6704-6717. http://dx.doi.org/10.1021/jm500739f.
24. Gunatilleke SS, Calvet CM, Johnston JB, Chen CK, Erenburg G, Gut J, Engel JC, Ang KK, Mulvaney J, Chen S, Arkin MR, McKerrow JH, Podust LM. 2012. Diverse inhibitor chemotypes targeting Trypanosoma cruzi CYP51. PLoS Negl Trop Dis 6:e1736. http://dx.doi.org/10.1371/journal.pntd.0001736.
25. Kraus JM, Tatipaka HB, McGuffin SA, Chennamaneni NK, Karimi M, Arif J, Verlinde CL, Buckner FS, Gelb MH. 2010. Second generation analogues of the cancer drug clinical candidate tipifarnib for anti-Chagas disease drug discovery. J Med Chem 53:3887-3898. http://dx.doi.org/10.1021/jm9013136.
26. Suryadevara PK, Racherla KK, Olepu S, Norcross NR, Tatipaka HB, Arif JA, Planer JD, Lepesheva GI, Verlinde CL, Buckner FS, Gelb MH. 2013. Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14alphademethylase as anti-Chagas disease agents. Bioorg Med Chem Lett 23:6492-6499. http://dx.doi.org/10.1016/j.bmcl.2013.08.015.
27. Martinez-Diaz RA, Escario JA, Nogal-Ruiz JJ, Gomez-Barrio A. 2001. Biological characterization of Trypanosoma cruzi strains. Mem Inst Oswaldo Cruz 96:53-59. http://dx.doi.org/10.1590/S0074-02762001000100006.
28. Moraes CB, Giardini MA, Kim H, Franco CH, Araujo-Junior AM, Schenkman S, Chatelain E, Freitas-Junior LH. 2014. Nitroheterocyclic compounds are more efficacious than CYP51 inhibitors against Trypanosoma cruzi: implications for Chagas disease drug discovery and development. Sci Rep 4:4703. http://dx.doi.org/10.1038/srep04703.
29. Tarleton RL, Zhang L. 1999. Chagas disease etiology: autoimmunity or parasite persistence? Parasitol Today 15:94-99. http://dx.doi.org/10.1016/S0169-4758 (99) 01398-8.
30. Urbina JA. 1999. Chemotherapy of Chagas' disease: the how and the why. J Mol Medicine 77:332-338. http://dx.doi.org/10.1007/s001090050359.
31. Marin-Neto JA, Rassi A, Jr, Avezum A, Jr, Mattos AC, Rassi A, Morillo CA, Sosa-Estani S, Yusuf S, BENEFIT Investigators. 2009. The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease. Mem Inst Oswaldo Cruz 104(Suppl 1):319-324. http://dx.doi.org/10.1590/S0074-02762009000900042.
32. Britto CC. 2009. Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations. Mem Inst Oswaldo Cruz 104(Suppl 1):122-135. http://dx.doi.org/10.1590/S0074-027620090 00900018.
33. Ferraz ML, Gazzinelli RT, Alves RO, Urbina JA, Romanha AJ. 2007. The anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole. Antimicrob Agents Chemother 51:1359-1364. http://dx.doi.org/10.1128/AAC.01170-06.
34. Molina J, Martins-Filho O, Brener Z, Romanha AJ, Loebenberg D, Urbina JA. 2000. Activities of the triazole derivative SCH 56592 (posaconazole) against drug-resistant strains of the protozoan parasite Trypanosoma (Schizotrypanum) cruzi in immunocompetent and immunosuppressed murine hosts. Antimicrob Agents Chemother 44:150-155. http://dx.doi.org/10.1128/AAC.44.1.150-155.2000.
35. Urbina JA, Payares G, Sanoja C, Lira R, Romanha AJ. 2003. In vitro and in vivo activities of ravuconazole on Trypanosoma cruzi, the causative agent of Chagas disease. Int J Antimicrob Agents 21:27-38. http://dx.doi.org/10.1016/S0924-8579 (02) 00273-X.
36. Cohen NR, Lobritz MA, Collins JJ. 2013. Microbial persistence and the road to drug resistance. Cell Host Microbe 13:632-642. http://dx.doi.org/10.1016/j.chom.2013.05.009.
37. Buckner FS, Bahia MT, Suryadevara PK, White KL, Shackleford DM, Chennamaneni NK, Hulverson MA, Laydbak JU, Chatelain E, Scandale I, Verlinde CL, Charman SA, Lepesheva GI, Gelb MH. 2012. Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib. Antimicrob Agents Chemother 56:4914-4921. http://dx.doi.org/10.1128/AAC.06244-11.
38. Ferraz ML, Gazzinelli RT, Alves RO, Urbina JA, Romanha AJ. 2009. Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection. Antimicrob Agents Chemother 53:174-179. http://dx.doi.org/10.1128/AAC.00779-08.