TY - JOUR
T1 - 3-Arylidene-N-hydroxyoxindoles
T2 - A New Class of Compounds Endowed with Antitumor Activity
AU - Musso, Loana
AU - Cincinelli, Raffaella
AU - Zuco, Valentina
AU - De Cesare, Michelandrea
AU - Zunino, Franco
AU - Fallacara, Anna Lucia
AU - Botta, Maurizio
AU - Dallavalle, Sabrina
PY - 2016/8/19
Y1 - 2016/8/19
N2 - A series of compounds containing the N-hydroxyoxindole scaffold were synthesized and evaluated for antitumor activity. The compounds showed potent antiproliferative activity against the wild-type p53 IGROV-1 ovarian carcinoma cell line and considerably lower efficacy against the mutant IGROV-1/Pt1 subline that lacks p53 function. The differential response of ovarian carcinoma cells depending on p53 status was also reflected in the varied susceptibility to apoptosis of the treated cell lines. These results support a role for the p53 transcription factor as a determinant of cytotoxicity. The therapeutic potential of the most promising compound of the series was evaluated in the treatment of an IGROV-1 xenograft growing as ascitic tumor in mice. Using intraperitoneal administration, daily treatment with the compound for four weeks produced a significant delay in the onset of ascites.
AB - A series of compounds containing the N-hydroxyoxindole scaffold were synthesized and evaluated for antitumor activity. The compounds showed potent antiproliferative activity against the wild-type p53 IGROV-1 ovarian carcinoma cell line and considerably lower efficacy against the mutant IGROV-1/Pt1 subline that lacks p53 function. The differential response of ovarian carcinoma cells depending on p53 status was also reflected in the varied susceptibility to apoptosis of the treated cell lines. These results support a role for the p53 transcription factor as a determinant of cytotoxicity. The therapeutic potential of the most promising compound of the series was evaluated in the treatment of an IGROV-1 xenograft growing as ascitic tumor in mice. Using intraperitoneal administration, daily treatment with the compound for four weeks produced a significant delay in the onset of ascites.
KW - antiproliferative activity
KW - antitumor agents
KW - apoptosis
KW - N-hydroxyoxindole
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=84983239017&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84983239017&partnerID=8YFLogxK
U2 - 10.1002/cmdc.201600225
DO - 10.1002/cmdc.201600225
M3 - Article
C2 - 27311681
AN - SCOPUS:84983239017
SP - 1700
EP - 1704
JO - ChemMedChem
JF - ChemMedChem
SN - 1860-7179
ER -