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.
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.
Maggio
Benedetta
B
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Raffa
Demetrio
D
Raimondi
Maria Valeria
MV
Cascioferro
Stella
S
Plescia
Fabiana
F
Tolomeo
Manlio
M
Barbusca
Eleonora
E
Cannizzo
Giuliana
G
Mancuso
Salvatrice
S
Daidone
Giuseppe
G
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*
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