3-Arylidene-N-hydroxyoxindoles: A New Class of Compounds Endowed with Antitumor Activity.
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.
Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133, Milano, Italy.
Loana
L
Musso
Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133, Milano, Italy.
Raffaella
R
Cincinelli
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Via Amadeo 42, 20133, Milano, Italy.
Valentina
V
Zuco
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Via Amadeo 42, 20133, Milano, Italy.
Michelandrea
M
De Cesare
Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS - Istituto Nazionale dei Tumori, Via Amadeo 42, 20133, Milano, Italy.
Franco
F
Zunino
Department of Biotechnology Chemistry and Pharmaceutical Science, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.
Anna Lucia
AL
Fallacara
Department of Biotechnology Chemistry and Pharmaceutical Science, University of Siena, Via Aldo Moro 2, 53100, Siena, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, BioLife Science Building, Suite 333, 1900 North 12th Street, Philadelphia, PA, 19122, USA.
Maurizio
M
Botta
Department of Food, Environmental and Nutritional Sciences, Division of Chemistry and Molecular Biology, University of Milan, via Celoria 2, 20133, Milano, Italy. sabrina.dallavalle@unimi.it.
Sabrina
0000-0002-8813-8922
S
Dallavalle
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007211:Indoles
N-hydroxyoxindole; antiproliferative activity; antitumor agents; apoptosis; p53