1,012
Views
25
CrossRef citations to date
0
Altmetric
Research Article

Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors

, , , , , & show all
Pages 1184-1191 | Received 01 Sep 2015, Accepted 06 Oct 2015, Published online: 16 Nov 2015

References

  • http://www.who.int/neglected_diseases/diseases/en/
  • Barrett MP, Burchmore RJS, Stich A, et al. The trypanosomiases. Lancet 2003;362:1469–80
  • http://www.who.int/mediacentre/factsheets/fs259/en/
  • Caffrey CR, Hansell E, Lucas KD, et al. Active site mapping, biochemical properties and subcellular localization of rhodesain, the major cysteine protease of Trypanosoma brucei rhodesiense. Mol Biochem Parasitol 2001;118:61–73
  • Ettari R, Tamborini L, Angelo IC, et al. Inhibition of rhodesain as a novel therapeutic modality for human African trypanosomiasis. J Med Chem 2013;56:5637–58
  • McShan D, Kathman S, Lowe B, et al. Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain. Bioorg Med Chem Lett 2015;25:4509-12
  • Jefferson T, McShan D, Warfield J, Ogungbe IV. Screening and identification of inhibitors of Trypanosoma brucei cathepsin L with antitrypanosomal activity. Chem Biol Drug Des 2015. [Epub ahead of print]. doi:10.1111/cbdd.12628
  • Micale N, Ettari R, Schirmeister T, et al. Novel 2H-isoquinolin-3-ones as antiplasmodial falcipain-2 inhibitors. Bioorg Med Chem 2009;17:6505–11
  • (a) Micale N, Kozikowski AP, Ettari R, et al. Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents. J Med Chem 2006;49:3064–7. (b) Ettari R, Nizi E, Di Francesco ME, et al. Development of peptidomimetics with a vinyl sulfone warhead as irreversible falcipain-2 inhibitors. J Med Chem 2008;51:988–96. (c) Ettari R, Nizi E, Di Francesco ME, et al. Nonpeptidic vinyl and allyl phosphonates as falcipain-2 inhibitors. ChemMedChem 2008;3:1030–3. (d) Ettari R, Micale N, Schirmeister T, et al. Novel peptidomimetics containing a vinyl ester moiety as highly potent and selective falcipain-2 inhibitors. J Med Chem 2009;52: 2157–60
  • (a) Ettari R, Zappalà M, Micale N, et al. Synthesis of novel peptidomimetics as inhibitors of protozoan cysteine proteases falcipain-2 and rhodesain. Eur J Med Chem 2010;45:3228–33. (b) Ettari R, Zappalà M, Micale N, et al. Peptidomimetics containing a vinyl ketone warhead as falcipain-2 inhibitors. Eur J Med Chem 2011;46:2058–65. (c) Ettari R, Micale N, Grazioso G, et al. Synthesis and molecular modeling studies on derivatives of a highly potent peptidomimetic vinyl ester as falcipain-2 inhibitor. ChemMedChem 2012;7:1594–600. (d) Grazioso G, Legnani L, Toma L, et al. Mechanism of falcipain-2 inhibition by a,b-unsaturated benzo[1,4]diazepin-2-one methyl ester. JCAMD 2012;26:1035–43
  • Bova F, Ettari R, Micale N, et al. Constrained peptidomimetics as antiplasmodial falcipain-2 inhibitors. Bioorg Med Chem 2010;18:4928–38
  • (a) Ettari R, Tamborini L, Angelo IC, et al. Development of novel inhibitors of rhodesain with a 3-bromo-isoxazoline warhead. ChemMedChem 2013;8:2070–6. (b) Ettari R, Pinto A, Tamborini L, et al. Synthesis and biological evaluation of papain-family cathepsin L-like cysteine protease inhibitors containing a 1,4-benzodiazepine scaffold, as antiprotozoan agents. ChemMedChem 2014;9:1817–25. (c) Ettari R, Pinto A, Previti S, et al. Development of novel dipeptide-like rhodesain inhibitors containing the 3-bromoisoxazoline warhead in a constrained conformation. Bioorg Med Chem 2015. [Epub ahead of print]. doi:10.1016/j.bmc.2015.09.029
  • De Amici M, Magri P, De Micheli C, et al. Nitrile oxides in medicinal chemistry. Chemoenzymic synthesis of chiral heterocyclic derivatives.. J Org Chem 1992;57:2825–9
  • Conti P, De Amici M, Pinto A, et al. Synthesis of 3-hydroxy- and 3-carboxy-?2-isoxazoline amino acids and evaluation of their interaction with GABA receptors and transporters. Eur J Org Chem 2006;24:5533–42
  • Breuning A, Degel B, Schulz F, et al. Michael acceptor based antiplasmodial and antitrypanosomal cysteine protease inhibitors with unusual amino acids. J Med Chem 2010;53:1951–63
  • Vicik R, Hoerr V, Glaser M, et al. Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents. Bioorg Med Chem Lett 2006;16:2753–7
  • Ludewig S, Kossner M, Schiller M, et al. Enzyme kinetics and hit validation in fluorimetric protease assays. Curr Top Med Chem 2010;10:368–82
  • Vicik R, Busemann M, Gelhaus C, et al. Aziridide-based inhibitors of cathepsin L: synthesis, inhibition activity, and docking studies. ChemMedChem 2006;1:1126–41
  • Baltz T, Baltz D, Giroud C, Crocket J. Cultivation in semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. EMBO J 1985;4:1273–7
  • Räz B, Iten M, Grether-Bühler Y, et al. The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T.b. rhodesiense and T.b. gambiense) in vitro. Acta Trop 1997;68:139–47
  • Merschjohann K, Sporer F, Steverding D, Wink M. In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense. Planta Med 2001;67:623–7
  • Huber W, Koella JC. A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites. Acta Trop 1993;55:257–61

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.