Substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones with antitumor activity. In depth study of the effect on growth of breast cancer cells.
The synthesis of new substituted E-3-(3-indolylmethylene)-1,3-dihydroindol-2-ones is reported. The antitumor activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. Structure-activity relationships are discussed. The action of selected compounds was investigated in MCF-7 breast cancer cells. The ability of these derivatives to inhibit cellular proliferation was accompanied by increased level of p53 and its transcriptional targets p21 and Bax, interference in the cell cycle progression with cell accumulation in the G2/M phase, and activation of apoptosis.
Andreani
Aldo
A
Dipartimento di Scienze Farmaceutiche, Universita di Bologna, Bologna, Italy. aldo.andreani@unibo.it
Bellini
Stefania
S
Burnelli
Silvia
S
Granaiola
Massimiliano
M
Leoni
Alberto
A
Locatelli
Alessandra
A
Morigi
Rita
R
Rambaldi
Mirella
M
Varoli
Lucilla
L
Calonghi
Natalia
N
Cappadone
Concettina
C
Zini
Maddalena
M
Stefanelli
Claudio
C
Masotti
Lanfranco
L
Shoemaker
Robert H
RH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D054697:Cytostatic Agents; D003603:Cytotoxins; D007211:Indoles; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein