Front Cover: Synthesis, Crystallization Studies, and in vitro Characterization of Cinnamic Acid Derivatives as SmHDAC8 Inhibitors for the Treatment of Schistosomiasis (ChemMedChem 15/2018). (13th August 2018)

• Record Type: Journal Article
• Authors: Bayer, Theresa; Chakrabarti, Alokta; Lancelot, Julien; Shaik, Tajith B.; Hausmann, Kristin; Melesina, Jelena; Schmidtkunz, Karin; Marek, Martin; Erdmann, Frank; Schmidt, Matthias; Robaa, Dina; Romier, Christophe; Pierce, Raymond J.; Jung, Manfred; Sippl, Wolfgang
• Is Part Of: ChemMedChem. Volume 13:Number 15(2018)
• Page Start: 1488
• Page End: 1488
• Publication Date: 2018-08-13
• Subjects: crystal structures -- docking -- HDAC -- hydroxamic acid -- schistosomiasis; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201800494
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The Front Cover reflects the structure‐guided optimization of histone deacetylase 8 (smHDAC8) inhibitors active against the human parasite Schistosoma mansoni . Starting from a cocrystallized fragment‐like hit, structure‐based design and in vitro testing resulted in nanomolar smHDAC8 inhibitors with good selectivity over the predominantly expressed human HDAC1 and 6 isoforms. Four X‐ray structures of smHDAC8 complexes are reported including the one illustrated. The developed inhibitor showed significant, dose‐dependent killing of the schistosome larvae and markedly impaired egg laying of adult worm pairs maintained in culture. More information can be found in the Full Paper by Wolfgang Sippl et al. on page 1517 in Issue 15, 2018 (DOI: 10.1002/cmdc.201800238 ).