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.

3-Arylidene-N-hydroxyoxindoles : a new class of compounds endowed with antitumor activity / L. Musso, R. Cincinelli, V. Zuco, M. Decesare, F. Zunino, A.L. Fallacara, M. Botta, S. Dallavalle. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 11:16(2016), pp. 1700-1704. ((Intervento presentato al 23. convegno National Meeting of the Medicinal-Chemistry-Division of the Italian-Chemical-Society (DCF-SCI) tenutosi a Salerno nel 2015 [10.1002/cmdc.201600225].

3-Arylidene-N-hydroxyoxindoles : a new class of compounds endowed with antitumor activity

L. Musso
Primo
;
R. Cincinelli
Secondo
;
S. Dallavalle
2016

Abstract

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.
Antiproliferative activity; Antitumor agents; Apoptosis; N-hydroxyoxindole; P53
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/06 - Chimica Organica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/431069
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