Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors

Wünsch M, Senger J, Schultheisz P, Schwarzbich S, Schmidtkunz K, Michalek C, Klaß M, Goskowitz S, Borchert P, Praetorius L, Sippl W, et al. (2017)
ChemMedChem 12(24): 2044-2053.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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DOI
Autor*in
Wünsch, MatthiasUniBi; Senger, Johanna; Schultheisz, Philipp; Schwarzbich, Sabrina; Schmidtkunz, Karin; Michalek, CarmelaUniBi; Klaß, MichaelaUniBi; Goskowitz, Stefanie; Borchert, Philipp; Praetorius, Lucas; Sippl, Wolfgang; Jung, Manfred
Alle
Einrichtung
Fakultät für Chemie > Organische Chemie III
Abstract / Bemerkung
As histone deacetylases (HDACs) play an important role in the treatment of cancer, their selective inhibition has been the subject of various studies. These continuous investigations have given rise to a large collection of pan- and selective HDAC inhibitors, containing diverse US Food and Drug Administration (FDA)-approved representatives. In previous studies, a class of alkyne-based HDAC inhibitors was presented. We modified this scaffold in two previously neglected regions and compared their cytotoxicity and affinity toward HDAC1, HDAC6, and HDAC8. We were able to show that R-configured propargylamines contribute to increased selectivity for HDAC6. Docking studies on available HDAC crystal structures were carried out to rationalize the observed selectivity of the compounds. Substitution of the aromatic portion by a thiophene derivative results in high affinity and low cytotoxicity, indicating an improved drug tolerance.
Stichworte
cancer; heterocycles; histone deacetylase; inhibitors; propargylamine
Erscheinungsjahr
2017
Zeitschriftentitel
ChemMedChem
Band
12
Ausgabe
24
Seite(n)
2044-2053
ISSN
1860-7179
eISSN
1860-7187
Page URI
https://pub.uni-bielefeld.de/record/2917176

Zitieren

Wünsch M, Senger J, Schultheisz P, et al. Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors. ChemMedChem. 2017;12(24):2044-2053.
Wünsch, M., Senger, J., Schultheisz, P., Schwarzbich, S., Schmidtkunz, K., Michalek, C., Klaß, M., et al. (2017). Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors. ChemMedChem, 12(24), 2044-2053. doi:10.1002/cmdc.201700550
Wünsch, Matthias, Senger, Johanna, Schultheisz, Philipp, Schwarzbich, Sabrina, Schmidtkunz, Karin, Michalek, Carmela, Klaß, Michaela, et al. 2017. “Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors”. ChemMedChem 12 (24): 2044-2053.
Wünsch, M., Senger, J., Schultheisz, P., Schwarzbich, S., Schmidtkunz, K., Michalek, C., Klaß, M., Goskowitz, S., Borchert, P., Praetorius, L., et al. (2017). Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors. ChemMedChem 12, 2044-2053.
Wünsch, M., et al., 2017. Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors. ChemMedChem, 12(24), p 2044-2053.
M. Wünsch, et al., “Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors”, ChemMedChem, vol. 12, 2017, pp. 2044-2053.
Wünsch, M., Senger, J., Schultheisz, P., Schwarzbich, S., Schmidtkunz, K., Michalek, C., Klaß, M., Goskowitz, S., Borchert, P., Praetorius, L., Sippl, W., Jung, M., Sewald, N.: Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors. ChemMedChem. 12, 2044-2053 (2017).
Wünsch, Matthias, Senger, Johanna, Schultheisz, Philipp, Schwarzbich, Sabrina, Schmidtkunz, Karin, Michalek, Carmela, Klaß, Michaela, Goskowitz, Stefanie, Borchert, Philipp, Praetorius, Lucas, Sippl, Wolfgang, Jung, Manfred, and Sewald, Norbert. “Structure-Activity Relationship of Propargylamine-Based HDAC Inhibitors”. ChemMedChem 12.24 (2017): 2044-2053.

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