Front Cover: Structure‐Based Design, Synthesis, and Biological Evaluation of Triazole‐Based smHDAC8 Inhibitors (ChemMedChem 7/2020). (1st April 2020)

• Record Type: Journal Article
• Authors: Kalinin, Dmitrii V.; Jana, Sunit K.; Pfafenrot, Maxim; Chakrabarti, Alokta; Melesina, Jelena; Shaik, Tajith B.; Lancelot, Julien; Pierce, Raymond J.; Sippl, Wolfgang; Romier, Christophe; Jung, Manfred; Holl, Ralph
• Is Part Of: ChemMedChem. Volume 15:Number 7(2020)
• Page Start: 559
• Page End: 559
• Publication Date: 2020-04-01
• Subjects: Schistosoma mansoni -- histone deacetylases -- triazole derivatives -- crystal structures -- molecular docking studies; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201000139
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The Front Cover shows the X‐ray crystal structure of the novel antiparasitic target Schistosoma mansoni histone deacetylase 8 (smHDAC8) in complex with our developed triazole‐based inhibitor. The inhibitor, whose structural formula is displayed top right, is the result of chemical modifications of the triazole‐based hit compound (top left), which were guided by crystallographic as well as molecular docking studies. Apart from being a nanomolar smHDAC8 inhibitor, the developed triazole shows a unique selectivity profile over the major human HDACs. The revealed key interactions between the inhibitor and the enzyme′s active site could be further utilized in the search for novel drugs for the treatment of schistosomiasis. More information can be found in the Full Paper by Ralph Holl et al. .