title: Chalcones, semicarbazones and pyrazolines as inhibitors of cathepsins B, H and L.
abstract: Cathepsin B [EC 3.4.22.1], cathepsin H [EC 3.4.22.16] and cathepsin L [EC 3.4.22.15] are the most versatile lysosomal cysteine proteases and are responsible for intracellular protein degradation. These are involved in a number of pathological conditions including tissue degenerative processes. In the present work, we report the synthesis and systematic evaluation of differently substituted chalcones, chalconesemicarbazones, and diarylpyrazolines on cathepsins B, H and L activity. It was found that after a preliminary screening as cysteine protease inhibitors, chalconesemicarbazones were better inhibitors to these cysteine proteases than diarylpyrazolines followed by chalcones. All the synthesized compounds were identified as the best inhibitors to cathepsin L followed by cathepsin B and then cathepsin H. The results are compared with docking studies and it was found that all the compounds resulted in decrease in energy while interacting with the active site of the enzyme.
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra 136119, Haryana, 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, Haryana, India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Kaur
mesh_terms: D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation; D007527:Isoenzymes; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D059748:Proteolysis / Q000187:drug effects; D012664:Semicarbazones / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D007527:Isoenzymes; D011480:Protease Inhibitors; D012664:Semicarbazones; D002403:Cathepsins
keywords: Cathepsin B; Cathepsin H; Cathepsin L; Inhibitors