Solution phase synthesis of a combinatorial library of chalcones and flavones as potent cathepsin V inhibitors.
Cathepsin V is a papain-like cysteine protease. It is involved in the control of human T cells (responsible for cell immunity), and presents the largest elastolytic activity among the proteolytic enzymes. Therefore, cathepsin V is a potential molecular target for the treatment of atherosclerosis. In the present work, natural flavonoids were screened against cathepsin V, and two flavones were identified as potent inhibitors of cathepsin V. On the basis of this result, a combinatorial library of chalcones and flavones was prepared, in solution phase employing a scavenger reagent, and fully evaluated.
Alvim
Joel
J
Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
Severino
Richele P
RP
Marques
Emerson F
EF
Martinelli
Ariane M
AM
Vieira
Paulo C
PC
Fernandes
João B
JB
da Silva
M Fatima das G F
MF
Corrêa
Arlene G
AG
D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D012996:Solutions; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects
D047188:Chalcones; D015853:Cysteine Proteinase Inhibitors; D047309:Flavones; D012996:Solutions; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C117627:CTSV protein, human