Design, synthesis and docking studies of bischalcones based quinazoline-2(1H)-ones and quinazoline-2(1H)-thiones derivatives as novel inhibitors of cathepsin B and cathepsin H

作者：Raghav Neera^*; Singh Mamta

来源：European Journal of Pharmaceutical Sciences, 2014, 54: 28-39.

DOI：10.1016/j.ejps.2013.12.018

• Cathepsin B
• Cathepsin H
• Non-peptidyl inhibitors
• Cancer progression
• Bischalcones and their quinazoline-2(1H)-one and quinazoline-2(1H)-thione derivative

A direct correlation between cancer progression and cathepsin expression has engrossed extensive consideration of these enzymes as potential drug targets for anticancer therapies. The present work is emphasized on potential therapeutic impact of 27 compounds on cathepsin B and cathepsin H, two significant lysosomal cysteine cathepsins involved in tumor progression and invasion. Bischalcones and their quinazoline-2(1H)-one and quinazoline-2(1H)-thione derivatives have been evaluated as potent inhibitors of cathepsin B and cathepsin H. Results exposed that bischalcones and their quinazoline-2(1H)-thione derivative inhibited cathepsin B and cathepsin H in a competitive manner whereas both cathepsins were inhibited in a non-competitive manner by quinazoline-2(1H)-one derivative. The experimental studies were compared with in silico docking results conducted with the help of iGemdock. The compounds under investigation add to the existing knowledge of non-peptidyl inhibitors of cathepsins B and H for anticancer drug development and chemotherapy.

• 出版日期2014-4-11