Pyrano[2,3-e]isoindol-2-ones, new angelicin heteroanalogues.
A convenient synthesis of the pyrano[2,3-e]isoindol-2-one ring system, an heteroanalogue of angelicin, is reported. Our synthetic approach consists of the annelation of the pyran ring on the isoindole moiety using 5-dialkylamino- or 5-hydroxymethylene intermediates as building blocks. The photoantiproliferative activity of the new derivatives was studied. Some of them bearing the benzyl group at the 8 position were active with IC(50) in the micromolar range. Cell cytotoxicity involves apoptosis, alteration of cell cycle profile and membrane photodamage.
Barraja
Paola
P
Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy.
Spanò
Virginia
V
Patrizia
Diana
D
Carbone
Anna
A
Cirrincione
Girolamo
G
Vedaldi
Daniela
D
Salvador
Alessia
A
Viola
Giampietro
G
Dall'acqua
Francesco
F
D017209:Apoptosis; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D054833:Isoindoles / Q000494:pharmacology*; D019169:Jurkat Cells; D020014:K562 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D011714:Pyrans / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011564:Furocoumarins; D054833:Isoindoles; D011714:Pyrans; C011659:angelicin; D010100:Oxygen