Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit Trypanosoma brucei Pteridine Reductase in Support of Early-Stage Drug Discovery

Autor: Monica S. Sá, Rebecca C. Wade, Claudia Danielli Pereira Bertolacini, Puneet Saxena, Bruno dos Santos Pascoalino, Markus Wolf, Ulrike Wittig, Wolfgang Müller, William N. Hunter, Anabela Cordeiro-da-Silva, Maria Paola Costi, Ina Pöhner, Jeanette Reinshagen, Véronique Hannaert, Nuno Santarém, Pasquale Linciano, Carolina B. Moraes, Philip Gribbon, Alice Dawson, Gesa Witt, Vanessa Fontana, Stefania Ferrari, Laura M. Alcântara, Giuseppe Cannazza, G. Landi, Bernhard Ellinger, Maria Kuzikov, Paul A.M. Michels, Stefano Mangani, David Costa, Erika Nerini, Birte Behrens, Sandra Lazzari, Cecilia Pozzi, Flavio Di Pisa, Lucio H. Freitas-Junior, Luca Costantino, Rosaria Luciani, Sheraz Gul

Publikováno v: ACS Omega, Vol 2, Iss 9, Pp 5666-5683 (2017)
'ACS Omega ', vol: 2, pages: 5666-5683 (2017)
Linciano, P, Dawson, A, Pöhner, I, Costa, D M, Sa, M S, Cordeiro-Da-Silva, A, Luciani, R, Gul, S, Witt, G, Ellinger, B, Kuzikov, M, Gribbon, P, Reinshagen, J, Wolf, M, Behrens, B, Hannaert, V, Michels, P A M, Nerini, E, Pozzi, C, Di Pisa, F, Landi, G, Santarem, N, Ferrari, S, Saxena, P, Lazzari, S, Cannazza, G, Freitas-Junior, L H, Moraes, C B, Pascoalino, B S, Alcantara, L M, Bertolacini, C P, Fontana, V, Wittig, U, Müller, W, Wade, R C, Hunter, W N, Mangani, S, Costantino, L & Costi, M P 2017, ' Exploiting the 2‑Amino-1,3,4-thiadiazole scaffold to inhibit trypanosoma brucei pteridine reductase in support of early-stage drug discovery ', ACS Omega, vol. 2, no. 9, pp. 5666-5683 . https://doi.org/10.1021/acsomega.7b00473

Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (T

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28935a981ead5c6c4b6475eb3f00313c
https://doi.org/10.1021/acsomega.7b00473

Virtual Screening Identification of Nonfolate Compounds, Including a CNS Drug, as Antiparasitic Agents Inhibiting Pteridine Reductase

Autor: Paul A.M. Michels, Domantas Motiejunas, Véronique Hannaert, M. Paola Costi, Samuele Calò, Erika Nerini, Shreedhara Gupta, Alberto Venturelli, Stefan Henrich, Sandra Lazzari, Rosaria Luciani, Stefania Ferrari, Rebecca C. Wade, Federica Morandi

Publikováno v: ResearcherID

Folate analogue inhibitors of Leishmania major pteridine reductase (PTR1) are potential antiparasitic drug candidates for combined therapy with dihydrofolate reductase (DHFR) inhibitors. To identify new molecules with specificity for PTR1, we carried

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30939b1c3bce24ea0e6f8146e0af3aa4
https://doi.org/10.1021/jm1010572

Sulphate Removal Induces a Major Conformational Change in Leishmania mexicana Pyruvate Kinase in the Crystalline State

Autor: Malcolm D. Walkinshaw, Hugh P. Morgan, Véronique Hannaert, Paul A.M. Michels, Linda A. Fothergill-Gilmore, Lindsay B. Tulloch

Publikováno v: Journal of Molecular Biology. 383:615-626

We report X-ray structures of pyruvate kinase from Leishmania mexicana (LmPYK) that are trapped in different conformations. These, together with the previously reported structure of LmPYK in its inactive (T-state) conformation, allow comparisons of t

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::44530e563a9b1e81c76252af42b95954
https://doi.org/10.1016/j.jmb.2008.08.037

Metabolic functions of glycosomes in trypanosomatids

Autor: Paul A.M. Michels, Véronique Hannaert, Murielle Herman, Frédéric Bringaud

Publikováno v: Biochimica et Biophysica Acta-Molecular Cell Research
Biochimica et Biophysica Acta-Molecular Cell Research, Elsevier, 2006, 1763 (12), pp.1463-77. ⟨10.1016/j.bbamcr.2006.08.019⟩

International audience; Protozoan Kinetoplastida, including the pathogenic trypanosomatids of the genera Trypanosoma and Leishmania, compartmentalize several important metabolic systems in their peroxisomes which are designated glycosomes. The enzyma

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f5777a1302c3cedd7617151258353c0

The Crystal Structure of Trypanosoma brucei Enolase: Visualisation of the Inhibitory Metal Binding Site III and Potential as Target for Selective, Irreversible Inhibition

Autor: Daniel J. Rigden, Mark H. Rider, Richard Charles Garratt, Didier Vertommen, Marcos V.A.S. Navarro, Paul A.M. Michels, M. T. S. Giotto, Véronique Hannaert

Publikováno v: Journal of Molecular Biology. 331:653-665

The glycolytic enzymes of the trypanosomatids, that cause a variety of medically and agriculturally important diseases, are validated targets for drug design. Design of species-specific inhibitors is facilitated by the availability of structural data

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78c1fccad0c52e4d66522d5c8b2768a5
https://doi.org/10.1016/s0022-2836(03)00752-6