TY - JOUR
T1 - New 1H-benzo[f]indazole-4,9-diones conjugated with C-protected amino acids and other derivatives
T2 - Synthesis and in vitro antiproliferative evaluation
AU - Molinari, Aurora
AU - Oliva, Alfonso
AU - Arismendi-Macuer, Marlene
AU - Guzmán, Leda
AU - Fuentealba, Mauricio
AU - Knox, Marcela
AU - Vinet, Raúl
AU - San Feliciano, Arturo
N1 - Funding Information:
This work was supported by the Comisi?n Nacional de Investigaci?n Cient?fica y Tecnol?gica CONICYT of Chile (Project FONDECYT 1100316) and by the Direcci?n de Investigaci?n de la Vicerrector?a de Investigaci?n y Estudios Avanzados de la Pontificia Universidad Cat?lica de Valpara?so, Chile (Projects DI 125.780/2010-2013, DI 037.383/2014 and DI 037.437/2015). M. Arismendi-Macuer acknowledges Doctoral Fellowship 21090246 from CONICYT and the Postdoctoral Grant from Vicerrector?a de Investigaci?n y Estudios Avanzados de la Pontificia Universidad Cat?lica de Valpara?so, Chile. R. Vinet acknowledges Grant CREAS CONICYT-REGIONAL, GORE Regi?n de Valpara?so, Chile [R12C1001].
Publisher Copyright:
© 2015 by The Authors.
PY - 2015/12/8
Y1 - 2015/12/8
N2 - 1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, L-alanine, L-phenylalanine and L-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9- dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, 1H-NMR and 13C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.
AB - 1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, L-alanine, L-phenylalanine and L-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9- dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, 1H-NMR and 13C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.
KW - 1,4-naphthoquinone
KW - 1H-benzoindazole
KW - Amino acid
KW - Pyrazole
UR - http://www.scopus.com/inward/record.url?scp=84954338616&partnerID=8YFLogxK
U2 - 10.3390/molecules201219809
DO - 10.3390/molecules201219809
M3 - Article
C2 - 26670225
AN - SCOPUS:84954338616
SN - 1420-3049
VL - 20
SP - 21924
EP - 21938
JO - Molecules
JF - Molecules
IS - 12
ER -