Anticancer activity of (1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and -purines against the MCF-7 cell line: Preliminary cDNA microarray studies.
Completing a SAR study, a series of (RS)-1- or 3-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H- or 9H-purines have been prepared. Their antiproliferative activities on MCF-7 cells are here presented and discussed. (RS)-6-Chloro-9-[1-(9H-9-fluorenylmethoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-9H-purine (28) is the most active (IC(50)=0.67+/-0.18 microM) of the series so far described. cDNA microarray technology reveals potential drug targets, which are mainly centred on apoptosis regulatory pathway genes.
Díaz-Gavilán
Mónica
M
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, c/Campus de Cartuja s/n, 18071 Granada, Spain.
Gómez-Vidal
José A
JA
Rodríguez-Serrano
Fernando
F
Marchal
Juan A
JA
Caba
Octavio
O
Aránega
Antonia
A
Gallo
Miguel A
MA
Espinosa
Antonio
A
Campos
Joaquín M
JM
D000080:Acetals / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D020411:Oligonucleotide Array Sequence Analysis; D010077:Oxazepines / Q000737:chemistry* / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000080:Acetals; D000970:Antineoplastic Agents; D010077:Oxazepines; D011687:Purines; D011743:Pyrimidines