Phenyldihydropyrazolones as Novel Lead Compounds Against Trypanosoma cruzi

Autor: Julianna Siciliano de Araújo, Louis Maes, Maria de Nazaré Correia Soeiro, Ignacio Cotillo, Iwan J. P. de Esch, Payman Sadek, Geert Jan Sterk, Stefan Kunz, Julio Martin, An Matheeussen, David G. Brown, Kristina M. Orrling, Marco Siderius, Ewald Edink, Susanne Schroeder, Hans Custers, Rob Leurs, Tiffany van de Meer, Maarten Sijm

Publikováno v: ACS Omega, Vol 4, Iss 4, Pp 6585-6596 (2019)
Sijm, M, Siciliano De Araújo, J, Kunz, S, Schroeder, S, Edink, E, Orrling, K M, Matheeussen, A, Van De Meer, T, Sadek, P, Custers, H, Cotillo, I, Martin, J J, Siderius, M, Maes, L, Brown, D G, De Nazaré Correia Soeiro, M, Sterk, G J, De Esch, I J P & Leurs, R 2019, ' Phenyldihydropyrazolones as Novel Lead Compounds Against Trypanosoma cruzi ', ACS Omega, vol. 4, no. 4, pp. 6585-6596 . https://doi.org/10.1021/acsomega.8b02847
ACS Omega, 4(4), 6585-6596. American Chemical Society
ACS Omega

As over 6 million people are infected with Chagas disease and only limited therapeutic options are available, there is an urgent need for novel drugs. The involvement of cyclic nucleotide phosphodiesterases (PDE) in the lifecycle and biological fitne

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9b5cce81802b5be7a51d2cb1a2a422c
https://doaj.org/article/10294135fb574185889e0e6a6942218f

Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity

Autor: An Matheeussen, Titilola D. Kalejaiye, Erik de Heuvel, A.R. Blaazer, A.K. Singh, Maikel Wijtmans, Wouter J. Mooij, Chris de Graaf, Maarten Sijm, Johan Veerman, Hermann Tenor, Chimed Jansen, Toine J. M. van den Bergh, David S. Bailey, Harry P. de Koning, Erin Balasubramaniam, Rob Leurs, Marco Siderius, David G. Brown, Iwan J. P. de Esch, Geert Jan Sterk, Louis Maes, Kristina M. Orrling, Daniel N. A. Tagoe, Hans Custers, Jane C. Munday, Ewald Edink

Publikováno v: Journal of Medicinal Chemistry
Journal of medicinal chemistry
Blaazer, A R, Singh, A K, De Heuvel, E, Edink, E, Orrling, K M, Veerman, J J N, Van Den Bergh, T, Jansen, C, Balasubramaniam, E, Mooij, W J, Custers, H, Sijm, M, Tagoe, D N A, Kalejaiye, T D, Munday, J C, Tenor, H, Matheeussen, A, Wijtmans, M, Siderius, M, De Graaf, C, Maes, L, De Koning, H P, Bailey, D S, Sterk, G J, De Esch, I J P, Brown, D G & Leurs, R 2018, ' Targeting a Subpocket in Trypanosoma brucei Phosphodiesterase B1 (TbrPDEB1) Enables the Structure-Based Discovery of Selective Inhibitors with Trypanocidal Activity ', Journal of Medicinal Chemistry, vol. 61, no. 9, pp. 3870-3888 . https://doi.org/10.1021/acs.jmedchem.7b01670
Journal of Medicinal Chemistry, 61(9), 3870-3888. American Chemical Society

Several trypanosomatid cyclic nucleotide phosphodiesterases (PDEs) possess a unique, parasite-specific cavity near the ligand-binding region that is referred to as the P-pocket. One of these enzymes, Trypanosoma brucei PDE B1 (TbrPDEB1), is considere

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f099b2fe26db21d0211e62360e1d7c87
https://pubmed.ncbi.nlm.nih.gov/29672041

Discovery of Novel Trypanosoma brucei Phosphodiesterase B1 Inhibitors by Virtual Screening against the Unliganded TbrPDEB1 Crystal Structure

Autor: Hermann Tenor, Albert J. Kooistra, Hengming Ke, Kristina M. Orrling, Thomas Seebeck, David S. Bailey, Chris de Graaf, Chimed Jansen, Rob Leurs, Iwan J. P. de Esch, Huanchen Wang

Publikováno v: Journal of Medicinal Chemistry, 2013(56), 2087-2096. American Chemical Society
Jansen, C, Wang, H, Kooistra, A J, de Graaf, C, Orrling, K M, Tenor, H, Seebeck, T, de Esch, I J P, Ke, H & Leurs, R 2013, ' Discovery of novel Trypanosoma brucei phosphodiesterase B1 inhibitors by virtual screening against the unliganded TbrPDEB1 crystal structure ', Journal of Medicinal Chemistry, vol. 2013, no. 56, pp. 2087-2096 . https://doi.org/10.1021/jm3017877

Trypanosoma brucei cyclic nucleotide phosphodiesterase B1 (TbrPDEB1) and TbrPDEB2 have recently been validated as new therapeutic targets for human African Trypanosomiasis by both genetic and pharmacological means. In this study we report the crystal

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82c9928c2eaf4436d29e11b8d1a3da59
https://doi.org/10.1021/jm3017877

Catechol Pyrazolinones as Trypanocidals: Fragment-Based Design, Synthesis, and Pharmacological Evaluation of Nanomolar Inhibitors of Trypanosomal Phosphodiesterase B1

Autor: Geert Jan Sterk, Paul England, Paul Cos, Erika van den Bogaart, Thomas Seebeck, Vreni Balmer, Anitha Shanmugham, Jean-Robert Ioset, Iwan J. P. de Esch, Xuan Lan Vu, Emily R. Adams, Eric Chatelain, Kristina M. Orrling, Chimed Jansen, Rob Leurs, Patrick Bregy, Andrea C. van de Stolpe, David S. Bailey, Johan Veerman, Stèphanie Zorg, Louis Maes

Publikováno v: Journal of Medicinal Chemistry, 55, 8745-8756. American Chemical Society
Journal of medicinal chemistry
Journal of medicinal chemistry, 55(20), 8745-8756. American Chemical Society
Orrling, K M, Jansen, C J W, Vu, X L, Balmer, V, Bregy, P, Shanmugham, A, England, P, Bailey, D, Cos, P, Maes, L, Adams, E, van den Bogaart, E, Chatelain, E, Ioset, J R, van de Stolpe, A, Zorg, S, Veerman, J, Seebeck, T, Sterk, G J, de Esch, I J P & Leurs, R 2012, ' Catechol pyrazolinones as trypanocidals: fragment-based design, synthesis, and pharmacological evaluation of nanomolar inhibitors of trypanosomal phosphodiesterase b1 ', Journal of Medicinal Chemistry, vol. 55, pp. 8745-8756 . https://doi.org/10.1021/jm301059b

Trypanosomal phosphodiesterases B1 and B2 (TbrPDEB1 and TbrPDEB2) play an important role in the life cycle of Trypanosoma brucei, the causative parasite of human African trypanosomiasis (HAT), also known as African sleeping sickness. We used homology

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::16156c197939817e91e94a7729d0918c
https://doi.org/10.1021/jm301059b

Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits

Autor: Anitha Shanmugham, Iwan J. P. de Esch, Ewald Edink, Louis Maes, A.R. Blaazer, Rob Leurs, David M. Bailey, Geert Jan Sterk, Paul England, Chimed Jansen, Marco Siderius, Kristina M. Orrling

Publikováno v: Journal of Biomolecular Screening, 20(1), 131-140. SAGE Publications Inc.
Journal of biomolecular screening
Blaazer, A R, Orrling, K M, Shanmugham, A, Jansen, C, Maes, L, Edink, E, Sterk, G J, Siderius, M, England, P, Bailey, D, de Esch, I J P & Leurs, R 2015, ' Fragment-based screening in tandem with phenotypic screening provides novel antiparasitic hits ', Journal of Biomolecular Screening, vol. 20, no. 1, pp. 131-140 . https://doi.org/10.1177/1087057114549735

Methods to discover biologically active small molecules include target-based and phenotypic screening approaches. One of the main difficulties in drug discovery is elucidating and exploiting the relationship between drug activity at the protein targe

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3cd461ce0c67625288e7ea4a714d5996
https://research.vu.nl/en/publications/aec5c47a-ce00-4001-95db-d41ab7ff01af