title: 1,5-Benzodiazepines XIV. Synthesis of new substituted 9H-bis-[1,2,4]triazolo[4,3-a:3',4'-d] [1,5]benzodiazepines and relate compounds endowed with in vitro cytotoxic properties.
abstract: A series of 11 new 9H-bis-[1,2,4]triazolo[4,3-a:3',4'-d] [1,5]benzodiazepine derivatives 8e-o was synthesized. Ten of these compounds (8e-m,o), along with four analogues (8a-d) (previously synthesized by us) were tested in vitro in order to evaluate their cytotoxic and anti-HIV-1 properties. In this connection other six original compounds, i.e., five 9-substituted compounds prepared starting from the 6,12-diphenylderivative 8c (compounds 10, 11, 12, 13a,b) and the bis-triazolone derivative 14, were synthesized and tested for the same purpose. While none of the 20 compounds tested exhibited any appreciable anti-HIV-1 activity, some of them exhibited interesting cytotoxic properties, the best results being shown by compounds 8c,d,k and 11 (CC(50) range=3-12 microM). Therefore, these four compounds were further evaluated for their antiproliferative activity against a panel of human tumor cell lines; actually, compounds 8d, 8k and 11 showed antiproliferative properties against either or both leukemia- and lymphoma-derived cell lines in the low micromolar range.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova, Italy. dbraccio@unige.it
authors.forename: Mario
authors.initials: M
authors.lastname: Di Braccio
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Grossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ceruti
authors.forename: Flavio
authors.initials: F
authors.lastname: Rocco
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.forename: Bernardetta
authors.initials: B
authors.lastname: Busonera
authors.forename: Marta
authors.initials: M
authors.lastname: Murreddu
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Marongiu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001569:Benzodiazepines