title: Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives.
abstract: Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observed difference among Dacarbazine and the active 4-triazenopyrazoles migth be explained admiting that these last compounds, differently by Dacarbazine, did not follow a mechanism of action based on the cytochrome P-450 induced demethylation. The most active compound 2d showed growth inhibition values of 97.8 and 99.4% against K562 and Raji cell lines respectively. Methotrexate inhibition values at 0.2 microM against the above cell lines were 86.7 and 75.1% respectively.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi, 32, 90123 Palermo, Italy. gdaidone@unipa.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daidone
authors.forename: Benedetta
authors.initials: B
authors.lastname: Maggio
authors.forename: Demetrio
authors.initials: D
authors.lastname: Raffa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Plescia
authors.forename: Domenico
authors.initials: D
authors.lastname: Schillaci
authors.forename: Maria
authors.initials: M
authors.lastname: Valeria Raimondi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D014227:Triazines; D003577:Cytochrome P-450 Enzyme System