title: 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.
abstract: 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.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119 India. Electronic address: nraghav.chem@gmail.com.
authors.forename: Neera
authors.initials: N
authors.lastname: Raghav
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119 India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Singh
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D056655:Cathepsin H / Q000037:antagonists & inhibitors*; D047188:Chalcones / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006041:Goats; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D047188:Chalcones; D004791:Enzyme Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D013871:Thiones; D002401:Cathepsin B; D056655:Cathepsin H
keywords: Bischalcones and their quinazoline-2(1H)-one and quinazoline-2(1H)-thione derivative; Cancer progression; Cathepsin B; Cathepsin H; Non-peptidyl inhibitors