Synthesis and evaluation of some semicarbazone- and thiosemicarbazone-based cathepsin B inhibitors

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• 作者：Neera Raghav ; Ravinder Kaur
• 关键词：Cathepsin B ; Inhibitors ; Semicarbazones ; Thiosemicarbazones ; Kinetic studies
• 刊名：Medicinal Chemistry Research
• 出版年：2014
• 出版时间：November 2014
• 年：2014
• 卷：23
• 期：11
• 页码：4669-4679
• 全文大小：1,257 KB
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• 作者单位：Neera Raghav (1)
  Ravinder Kaur (1)
  
  1. Department of Chemistry, Kurukshetra University, Kurukshetra, 132116, Haryana, India
  
• ISSN：1554-8120

文摘

In the present work, we report the synthesis and systematic evaluation of differently substituted semicarbazones and thiosemicarbazones on lysosomal cysteine protease, cathepsin B [3.4.22.1]. Thiosemicarbazones have been found to inhibit cathepsin B activity to a greater extent than semicarbazones. Among the differently functionalized semicarbazones (1a-j) and thiosemicarbazones (2a-j), chloro-substituted compounds have been found to inhibit cathepsin B most effectively with the K i value of 1.16?×?10? and 1.48?×?10??M, respectively. The designed derivatives have been found to be competitive inhibitors to cathepsin B. The results of docking experiments also show a decrease in energy after ligand–enzyme active site interaction supporting the designed compounds as inhibitors to cathepsin B.