Synthetic chalcone derivatives as inhibitors of cathepsins K and B, and their cytotoxic evaluation.
A series of chalcone derivatives, 1-15, were prepared by Claisen-Schmidt condensation and evaluated for their cytotoxicities on tumor cell lines and also against proteolytic enzymes such as cathepsins B and K. Of the compounds synthesized, (E)-3-(3,4-dimethoxyphenyl)-1-phenylprop-2-en-1-one (12), (E)-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one (13), (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (14), and (E)-3-(4-nitrophenyl)-1-phenylprop-2-en-1-one (15) showed significant cytotoxicities. The most effective compound was 15, which showed high cytotoxic activity with an IC50 value lower than 1 μg/ml, and no selectivity on the tumor cells evaluated. Substituents at C(4) of ring B were found to be essential for cytotoxicity. In addition, it was also demonstrated that some of these chalcones are moderate inhibitors of cathepsin K and have no activity against cathepsin B.
Department of Chemistry, State University of Goiás, 495, Anápolis, GO, Brazil; Department of Chemistry, Federal University of São Carlos, 13565-905, São Carlos, SP, Brazil.
Suelem Demuner
SD
Ramalho
Aline
A
Bernades
Giulio
G
Demetrius
Caridad
C
Noda-Perez
Paulo Cezar
PC
Vieira
Caio Yu
CY
Dos Santos
James Almada
JA
da Silva
Manoel Odorico
MO
de Moraes
Kristiana Cerqueira
KC
Mousinho
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056657:Cathepsin K / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D002599:Chalcone; D002401:Cathepsin B; D056657:Cathepsin K
Cathepsins; Chalcones; Cytotoxic activity