title: Synthesis of triazenoazaindoles: a new class of triazenes with antitumor activity.
abstract: Despite improvements in the treatment and prevention of cancer, the number of new diagnoses continues to rise; this has fuelled substantial interest in the development of new and effective chemotherapeutic agents. Compounds of the triazene class, such as dacarbazine, have been used in the clinical management of many cancer types including brain, leukemia, and melanoma. A new compound class bearing a triazenoazaindole scaffold was synthesized with the aim of identifying new antiproliferative agents. Compounds 5a-g and 6a-c were screened against a panel of human tumor cell lines, and two of them, 5e and 5f, showed cytotoxicity (GI(50) range: 2.2-8.2 μM) in all cell lines. These two compounds even maintained their cytotoxicity in some multidrug-resistant cell lines. Flow cytometry analysis demonstrated their ability to induce cell death by apoptosis with involvement of lysosomes.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Sezione di Chimica Farmaceutica e Biologica, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy. diana@unipa.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Diana
authors.forename: Antonina
authors.initials: A
authors.lastname: Stagno
authors.forename: Paola
authors.initials: P
authors.lastname: Barraja
authors.forename: Anna
authors.initials: A
authors.lastname: Carbone
authors.forename: Barbara
authors.initials: B
authors.lastname: Parrino
authors.forename: Francesco
authors.initials: F
authors.lastname: Dall'Acqua
authors.forename: Daniela
authors.initials: D
authors.lastname: Vedaldi
authors.forename: Alessia
authors.initials: A
authors.lastname: Salvador
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Olaf Georg
authors.initials: OG
authors.lastname: Issinger
authors.forename: Girolamo
authors.initials: G
authors.lastname: Cirrincione
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D014226:Triazenes / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D014226:Triazenes; D003606:Dacarbazine; D066246:ErbB Receptors