title: Antitumor activity of bis-indole derivatives.
abstract: This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy-2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice). In conclusion we demonstrated that this approach was successful, since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy. aldo.andreani@unibo.it
authors.forename: Aldo
authors.initials: A
authors.lastname: Andreani
authors.forename: Silvia
authors.initials: S
authors.lastname: Burnelli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Granaiola
authors.forename: Alberto
authors.initials: A
authors.lastname: Leoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Locatelli
authors.forename: Rita
authors.initials: R
authors.lastname: Morigi
authors.forename: Mirella
authors.initials: M
authors.lastname: Rambaldi
authors.forename: Lucilla
authors.initials: L
authors.lastname: Varoli
authors.forename: Laura
authors.initials: L
authors.lastname: Landi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Prata
authors.forename: Michael V
authors.initials: MV
authors.lastname: Berridge
authors.forename: Carole
authors.initials: C
authors.lastname: Grasso
authors.forename: Heinz-Herbert
authors.initials: HH
authors.lastname: Fiebig
authors.forename: Gerhard
authors.initials: G
authors.lastname: Kelter
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Burger
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kunkel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; C030374:indole; D044767:Ubiquitin-Protein Ligases