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Items: 1 to 50 of 72

1.

A new chemotype with promise against Trypanosoma cruzi.

Wang X, Cal M, Kaiser M, Buckner FS, Lepesheva GI, Sanford AG, Wallick AI, Davis PH, Vennerstrom JL.

Bioorg Med Chem Lett. 2019 Oct 31:126778. doi: 10.1016/j.bmcl.2019.126778. [Epub ahead of print]

PMID:
31706668
2.

Validation of Human Sterol 14α-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors.

Friggeri L, Hargrove TY, Wawrzak Z, Guengerich FP, Lepesheva GI.

J Med Chem. 2019 Nov 11. doi: 10.1021/acs.jmedchem.9b01485. [Epub ahead of print]

PMID:
31663733
3.

Successful Aspects of the Coadministration of Sterol 14α-Demethylase Inhibitor VFV and Benznidazole in Experimental Mouse Models of Chagas Disease Caused by the Drug-Resistant Strain of Trypanosoma cruzi.

Guedes-da-Silva FH, Batista DDGJ, Da Silva CF, Pavão BP, Batista MM, Moreira OC, Souza LRQ, Britto C, Rachakonda G, Villalta F, Lepesheva GI, Soeiro MNC.

ACS Infect Dis. 2019 Mar 8;5(3):365-371. doi: 10.1021/acsinfecdis.8b00253. Epub 2019 Jan 23.

PMID:
30625275
4.

Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae.

Friggeri L, Hargrove TY, Rachakonda G, Blobaum AL, Fisher P, de Oliveira GM, da Silva CF, Soeiro MNC, Nes WD, Lindsley CW, Villalta F, Guengerich FP, Lepesheva GI.

J Med Chem. 2018 Dec 13;61(23):10910-10921. doi: 10.1021/acs.jmedchem.8b01671. Epub 2018 Nov 30.

PMID:
30451500
5.

Binding of a physiological substrate causes large-scale conformational reorganization in cytochrome P450 51.

Hargrove TY, Wawrzak Z, Fisher PM, Child SA, Nes WD, Guengerich FP, Waterman MR, Lepesheva GI.

J Biol Chem. 2018 Dec 14;293(50):19344-19353. doi: 10.1074/jbc.RA118.005850. Epub 2018 Oct 16.

PMID:
30327430
6.

Sterol 14α-Demethylase Structure-Based Design of VNI (( R)- N-(1-(2,4-Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) Derivatives To Target Fungal Infections: Synthesis, Biological Evaluation, and Crystallographic Analysis.

Friggeri L, Hargrove TY, Wawrzak Z, Blobaum AL, Rachakonda G, Lindsley CW, Villalta F, Nes WD, Botta M, Guengerich FP, Lepesheva GI.

J Med Chem. 2018 Jul 12;61(13):5679-5691. doi: 10.1021/acs.jmedchem.8b00641. Epub 2018 Jun 25.

7.

CYP51 as drug targets for fungi and protozoan parasites: past, present and future.

Lepesheva GI, Friggeri L, Waterman MR.

Parasitology. 2018 Dec;145(14):1820-1836. doi: 10.1017/S0031182018000562. Epub 2018 Apr 12. Review.

8.

Antitrypanosomal and antileishmanial activity of prenyl-1,2,3-triazoles.

Porta EOJ, Jäger SN, Nocito I, Lepesheva GI, Serra EC, Tekwani BL, Labadie GR.

Medchemcomm. 2017 May 1;8(5):1015-1021. doi: 10.1039/C7MD00008A. Epub 2017 Mar 10.

9.

Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana.

Mwenechanya R, Kovářová J, Dickens NJ, Mudaliar M, Herzyk P, Vincent IM, Weidt SK, Burgess KE, Burchmore RJS, Pountain AW, Smith TK, Creek DJ, Kim DH, Lepesheva GI, Barrett MP.

PLoS Negl Trop Dis. 2017 Jun 16;11(6):e0005649. doi: 10.1371/journal.pntd.0005649. eCollection 2017 Jun.

10.

Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity.

Hargrove TY, Garvey EP, Hoekstra WJ, Yates CM, Wawrzak Z, Rachakonda G, Villalta F, Lepesheva GI.

Antimicrob Agents Chemother. 2017 Jun 27;61(7). pii: e00570-17. doi: 10.1128/AAC.00570-17. Print 2017 Jul.

11.

Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis.

Hargrove TY, Friggeri L, Wawrzak Z, Qi A, Hoekstra WJ, Schotzinger RJ, York JD, Guengerich FP, Lepesheva GI.

J Biol Chem. 2017 Apr 21;292(16):6728-6743. doi: 10.1074/jbc.M117.778308. Epub 2017 Mar 3.

12.

Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain.

Guedes-da-Silva FH, Batista DG, Da Silva CF, De Araújo JS, Pavão BP, Simões-Silva MR, Batista MM, Demarque KC, Moreira OC, Britto C, Lepesheva GI, Soeiro MN.

Antimicrob Agents Chemother. 2017 Mar 24;61(4). pii: e02098-16. doi: 10.1128/AAC.02098-16. Print 2017 Apr.

13.

Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design.

Hargrove TY, Friggeri L, Wawrzak Z, Sivakumaran S, Yazlovitskaya EM, Hiebert SW, Guengerich FP, Waterman MR, Lepesheva GI.

J Lipid Res. 2016 Aug;57(8):1552-63. doi: 10.1194/jlr.M069229. Epub 2016 Jun 16.

14.

Clinical Candidate VT-1161's Antiparasitic Effect In Vitro, Activity in a Murine Model of Chagas Disease, and Structural Characterization in Complex with the Target Enzyme CYP51 from Trypanosoma cruzi.

Hoekstra WJ, Hargrove TY, Wawrzak Z, da Gama Jaen Batista D, da Silva CF, Nefertiti AS, Rachakonda G, Schotzinger RJ, Villalta F, Soeiro Mde N, Lepesheva GI.

Antimicrob Agents Chemother. 2015 Dec 7;60(2):1058-66. doi: 10.1128/AAC.02287-15. Print 2016 Feb.

15.

Ligand tunnels in T. brucei and human CYP51: Insights for parasite-specific drug design.

Yu X, Nandekar P, Mustafa G, Cojocaru V, Lepesheva GI, Wade RC.

Biochim Biophys Acta. 2016 Jan;1860(1 Pt A):67-78. doi: 10.1016/j.bbagen.2015.10.015. Epub 2015 Oct 19.

16.

Different Therapeutic Outcomes of Benznidazole and VNI Treatments in Different Genders in Mouse Experimental Models of Trypanosoma cruzi Infection.

Guedes-da-Silva FH, Batista DG, da Silva CF, Meuser MB, Simões-Silva MR, de Araújo JS, Ferreira CG, Moreira OC, Britto C, Lepesheva GI, Soeiro Mde N.

Antimicrob Agents Chemother. 2015 Dec;59(12):7564-70. doi: 10.1128/AAC.01294-15. Epub 2015 Sep 28.

17.

Structure-Functional Characterization of Cytochrome P450 Sterol 14α-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs.

Hargrove TY, Wawrzak Z, Lamb DC, Guengerich FP, Lepesheva GI.

J Biol Chem. 2015 Sep 25;290(39):23916-34. doi: 10.1074/jbc.M115.677310. Epub 2015 Aug 12.

18.

VFV as a New Effective CYP51 Structure-Derived Drug Candidate for Chagas Disease and Visceral Leishmaniasis.

Lepesheva GI, Hargrove TY, Rachakonda G, Wawrzak Z, Pomel S, Cojean S, Nde PN, Nes WD, Locuson CW, Calcutt MW, Waterman MR, Daniels JS, Loiseau PM, Villalta F.

J Infect Dis. 2015 Nov 1;212(9):1439-48. doi: 10.1093/infdis/jiv228. Epub 2015 Apr 15.

19.

Dynamics of CYP51: implications for function and inhibitor design.

Yu X, Cojocaru V, Mustafa G, Salo-Ahen OM, Lepesheva GI, Wade RC.

J Mol Recognit. 2015 Feb;28(2):59-73. doi: 10.1002/jmr.2412. Epub 2015 Jan 20.

20.

Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents.

Papadopoulou MV, Bloomer WD, Lepesheva GI, Rosenzweig HS, Kaiser M, Aguilera-Venegas B, Wilkinson SR, Chatelain E, Ioset JR.

J Med Chem. 2015 Feb 12;58(3):1307-19. doi: 10.1021/jm5015742. Epub 2015 Jan 23.

21.

Sequence variation in CYP51A from the Y strain of Trypanosoma cruzi alters its sensitivity to inhibition.

Cherkesova TS, Hargrove TY, Vanrell MC, Ges I, Usanov SA, Romano PS, Lepesheva GI.

FEBS Lett. 2014 Nov 3;588(21):3878-85. doi: 10.1016/j.febslet.2014.08.030. Epub 2014 Sep 12.

22.

Structural basis for rational design of inhibitors targeting Trypanosoma cruzi sterol 14α-demethylase: two regions of the enzyme molecule potentiate its inhibition.

Friggeri L, Hargrove TY, Rachakonda G, Williams AD, Wawrzak Z, Di Santo R, De Vita D, Waterman MR, Tortorella S, Villalta F, Lepesheva GI.

J Med Chem. 2014 Aug 14;57(15):6704-17. doi: 10.1021/jm500739f. Epub 2014 Jul 29.

23.

Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents.

Suryadevara PK, Racherla KK, Olepu S, Norcross NR, Tatipaka HB, Arif JA, Planer JD, Lepesheva GI, Verlinde CL, Buckner FS, Gelb MH.

Bioorg Med Chem Lett. 2013 Dec 1;23(23):6492-9. doi: 10.1016/j.bmcl.2013.08.015. Epub 2013 Aug 12.

24.

Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

Lepesheva GI.

Expert Opin Drug Discov. 2013 Dec;8(12):1479-89. doi: 10.1517/17460441.2013.845554. Epub 2013 Sep 30. Review.

25.

Complexes of Trypanosoma cruzi sterol 14α-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: structural basis for pathogen selectivity.

Hargrove TY, Wawrzak Z, Alexander PW, Chaplin JH, Keenan M, Charman SA, Perez CJ, Waterman MR, Chatelain E, Lepesheva GI.

J Biol Chem. 2013 Nov 1;288(44):31602-15. doi: 10.1074/jbc.M113.497990. Epub 2013 Sep 18.

26.

In vitro and in vivo studies of the antiparasitic activity of sterol 14α-demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi.

Soeiro Mde N, de Souza EM, da Silva CF, Batista Dda G, Batista MM, Pavão BP, Araújo JS, Aiub CA, da Silva PB, Lionel J, Britto C, Kim K, Sulikowski G, Hargrove TY, Waterman MR, Lepesheva GI.

Antimicrob Agents Chemother. 2013 Sep;57(9):4151-63. doi: 10.1128/AAC.00070-13. Epub 2013 Jun 17.

27.

CYP51 structures and structure-based development of novel, pathogen-specific inhibitory scaffolds.

Hargrove TY, Kim K, de Nazaré Correia Soeiro M, da Silva CF, Batista DD, Batista MM, Yazlovitskaya EM, Waterman MR, Sulikowski GA, Lepesheva GI.

Int J Parasitol Drugs Drug Resist. 2012 Dec;2:178-186. Epub 2012 Jun 30.

28.

Antitrypanosomal lead discovery: identification of a ligand-efficient inhibitor of Trypanosoma cruzi CYP51 and parasite growth.

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.

J Med Chem. 2013 Mar 28;56(6):2556-67. doi: 10.1021/jm400012e. Epub 2013 Mar 13.

29.

VNI cures acute and chronic experimental Chagas disease.

Villalta F, Dobish MC, Nde PN, Kleshchenko YY, Hargrove TY, Johnson CA, Waterman MR, Johnston JN, Lepesheva GI.

J Infect Dis. 2013 Aug 1;208(3):504-11. doi: 10.1093/infdis/jit042. Epub 2013 Jan 31.

30.

Organocatalytic, enantioselective synthesis of VNI: a robust therapeutic development platform for Chagas, a neglected tropical disease.

Dobish MC, Villalta F, Waterman MR, Lepesheva GI, Johnston JN.

Org Lett. 2012 Dec 21;14(24):6322-5. doi: 10.1021/ol303092v. Epub 2012 Dec 7.

31.

Pharmacological characterization, structural studies, and in vivo activities of anti-Chagas disease lead compounds derived from tipifarnib.

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.

Antimicrob Agents Chemother. 2012 Sep;56(9):4914-21. doi: 10.1128/AAC.06244-11. Epub 2012 Jul 9.

32.

Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms.

Nes CR, Singha UK, Liu J, Ganapathy K, Villalta F, Waterman MR, Lepesheva GI, Chaudhuri M, Nes WD.

Biochem J. 2012 Apr 1;443(1):267-77. doi: 10.1042/BJ20111849.

33.

Structural complex of sterol 14α-demethylase (CYP51) with 14α-methylenecyclopropyl-Delta7-24, 25-dihydrolanosterol.

Hargrove TY, Wawrzak Z, Liu J, Waterman MR, Nes WD, Lepesheva GI.

J Lipid Res. 2012 Feb;53(2):311-20. doi: 10.1194/jlr.M021865. Epub 2011 Nov 30.

34.

Targeting Trypanosoma cruzi sterol 14α-demethylase (CYP51).

Lepesheva GI, Villalta F, Waterman MR.

Adv Parasitol. 2011;75:65-87. doi: 10.1016/B978-0-12-385863-4.00004-6. Review.

35.

Substrate preferences and catalytic parameters determined by structural characteristics of sterol 14alpha-demethylase (CYP51) from Leishmania infantum.

Hargrove TY, Wawrzak Z, Liu J, Nes WD, Waterman MR, Lepesheva GI.

J Biol Chem. 2011 Jul 29;286(30):26838-48. doi: 10.1074/jbc.M111.237099. Epub 2011 May 31.

36.
37.

Structural basis for conservation in the CYP51 family.

Lepesheva GI, Waterman MR.

Biochim Biophys Acta. 2011 Jan;1814(1):88-93. doi: 10.1016/j.bbapap.2010.06.006. Epub 2010 Jun 11. Review.

38.

Structural insights into inhibition of sterol 14alpha-demethylase in the human pathogen Trypanosoma cruzi.

Lepesheva GI, Hargrove TY, Anderson S, Kleshchenko Y, Furtak V, Wawrzak Z, Villalta F, Waterman MR.

J Biol Chem. 2010 Aug 13;285(33):25582-90. doi: 10.1074/jbc.M110.133215. Epub 2010 Jun 8.

39.

Crystal structures of Trypanosoma brucei sterol 14alpha-demethylase and implications for selective treatment of human infections.

Lepesheva GI, Park HW, Hargrove TY, Vanhollebeke B, Wawrzak Z, Harp JM, Sundaramoorthy M, Nes WD, Pays E, Chaudhuri M, Villalta F, Waterman MR.

J Biol Chem. 2010 Jan 15;285(3):1773-80. doi: 10.1074/jbc.M109.067470. Epub 2009 Nov 18.

40.

The first virally encoded cytochrome p450.

Lamb DC, Lei L, Warrilow AG, Lepesheva GI, Mullins JG, Waterman MR, Kelly SL.

J Virol. 2009 Aug;83(16):8266-9. doi: 10.1128/JVI.00289-09. Epub 2009 Jun 10.

41.

Indomethacin amides as a novel molecular scaffold for targeting Trypanosoma cruzi sterol 14alpha-demethylase.

Konkle ME, Hargrove TY, Kleshchenko YY, von Kries JP, Ridenour W, Uddin MJ, Caprioli RM, Marnett LJ, Nes WD, Villalta F, Waterman MR, Lepesheva GI.

J Med Chem. 2009 May 14;52(9):2846-53. doi: 10.1021/jm801643b.

42.

Rational modification of a candidate cancer drug for use against Chagas disease.

Kraus JM, Verlinde CL, Karimi M, Lepesheva GI, Gelb MH, Buckner FS.

J Med Chem. 2009 Mar 26;52(6):1639-47. doi: 10.1021/jm801313t. Erratum in: J Med Chem. 2009 Aug 13;52(15):4979. J Med Chem. 2009 Jul 23;52(14):4549.

43.

CYP51: A major drug target in the cytochrome P450 superfamily.

Lepesheva GI, Hargrove TY, Kleshchenko Y, Nes WD, Villalta F, Waterman MR.

Lipids. 2008 Dec;43(12):1117-25. doi: 10.1007/s11745-008-3225-y. Epub 2008 Sep 4.

44.

Sterol 14alpha-demethylase as a potential target for antitrypanosomal therapy: enzyme inhibition and parasite cell growth.

Lepesheva GI, Ott RD, Hargrove TY, Kleshchenko YY, Schuster I, Nes WD, Hill GC, Villalta F, Waterman MR.

Chem Biol. 2007 Nov;14(11):1283-93.

45.

Conformational dynamics in the F/G segment of CYP51 from Mycobacterium tuberculosis monitored by FRET.

Lepesheva GI, Seliskar M, Knutson CG, Stourman NV, Rozman D, Waterman MR.

Arch Biochem Biophys. 2007 Aug 15;464(2):221-7. Epub 2007 Jun 6.

46.

Biodiversity of CYP51 in trypanosomes.

Lepesheva GI, Hargrove TY, Ott RD, Nes WD, Waterman MR.

Biochem Soc Trans. 2006 Dec;34(Pt 6):1161-4.

PMID:
17073776
47.

Role of C-terminal sequence of cytochrome P450scc in folding and functional activity.

Strushkevich NV, Harnastai IN, Lepesheva GI, Usanov SA.

Biochemistry (Mosc). 2006 Sep;71(9):1027-34.

PMID:
17009958
48.

Sterol 14alpha-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms.

Lepesheva GI, Waterman MR.

Biochim Biophys Acta. 2007 Mar;1770(3):467-77. Epub 2006 Aug 2. Review.

49.

Mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in Trypanosoma brucei.

Zhou W, Lepesheva GI, Waterman MR, Nes WD.

J Biol Chem. 2006 Mar 10;281(10):6290-6. Epub 2006 Jan 12.

50.

A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases.

Lamb DC, Kim Y, Yermalitskaya LV, Yermalitsky VN, Lepesheva GI, Kelly SL, Waterman MR, Podust LM.

Structure. 2006 Jan;14(1):51-61.

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