title: Discovery of 8-methoxypyrazino[1,2-a]indole as a New Potent Antiproliferative Agent Against Human Leukemia K562 Cells. A Structure-Activity Relationship Study.
abstract: Identification of novel and selective anticancer agents remains an important and challenging goal in pharmacological research. The indole nucleus, frequently encountered as a molecular fragment in natural products and pharmaceutically active compounds, was employed as the initial building block for the synthesis of a series of pyrazino[1,2-a]indoles 1a-k, variably substituted at the 6, 7, 8 and 9-positions. Compound 1e, bearing the methoxy group at the 8-position of the pyrazino[1,2-a]indole nucleus was identified as a novel potent antiproliferative agent against the human chronic myelogenous leukemia K562 cell line, but it was much less active against several other cancer cell lines. Comparison of positional isomers indicated that moving the methoxy group from the 8- to the 7- or 6-position, to furnish compounds 1f and 1g, respectively, yielded inactive compounds. The analysis of structure-activity relationships observed in the series of investigated compounds may represent the basis for the design of more active molecules.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Ferrara, 44100 Ferrara, Italy.
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Maria Dora
authors.initials: MD
authors.lastname: Carrion
authors.forename: Olga
authors.initials: O
authors.lastname: Cruz-Lopez
authors.forename: Carlota Lopez
authors.initials: CL
authors.lastname: Cara
authors.forename: Delia
authors.initials: D
authors.lastname: Preti
authors.forename: Mojgan Aghazadeh
authors.initials: MA
authors.lastname: Tabrizi
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari