title: Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one.
abstract: The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The compound showed antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562 resistant cell lines markedly higher than etoposide and busulfan, respectively. Flow cytometry studies carried out on K562 cells allowed to establish that 15 induces G0-G1 phase arrest followed by apoptosis.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Maggio
authors.forename: Demetrio
authors.initials: D
authors.lastname: Raffa
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Raimondi
authors.forename: Stella
authors.initials: S
authors.lastname: Cascioferro
authors.forename: Fabiana
authors.initials: F
authors.lastname: Plescia
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Barbusca
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cannizzo
authors.forename: Salvatrice
authors.initials: S
authors.lastname: Mancuso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Daidone
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects*; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*
chemical_list: C534134:3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo(3,4-f)(1,2,3,5)tetrazepin-4(3H)-one; D001381:Azepines; D011720:Pyrazoles