title: Anticancer activity and cDNA microarray studies of a (RS)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine, and an acyclic (RS)-O,N-acetalic 6-chloro-7H-purine.
abstract: Completing a SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines was previously prepared. The most potent antiproliferative agent against the MCF-7 adenocarcinoma cell line that belongs to the benzoxazepine O,N-acetalic family is (RS)-9-[1-(9H-fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9H-purine (16, IC(50) = 0.67 ± 0.18 μM), whilst (RS)-7-{2-(N-hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7H-purine (37) shows the lowest IC(50) value between the family of acyclic O,N-acetals (IC(50) = 3.25 ± 0.23 μM). Moreover, 16 showed the better in vitro Therapeutic Index in breast cell lines (3.19), whilst 37 was found to be 3.69-fold more active against HT-29 human colon cancer cell line than versus IEC-6 normal rat intestinal epithelial cell line. The global apoptotic cells caused by 16 and 37 against MCF-7 were 80.08% and 54.85% of cell population after 48 h, respectively. cDNA microarray technology reveals potential drug targets, which are mainly centred on positive apoptosis regulatory pathway genes, and the repression of genes involved in carcinogenesis, proliferation and tumour invasion.
authors.affiliation: Departamento de Anatomía y Embriología Humana, Facultad de Medicina, Instituto de Biopatología y Medicina Regenerativa, 18071 Granada, Spain.
authors.forename: Octavio
authors.initials: O
authors.lastname: Caba
authors.forename: Mónica
authors.initials: M
authors.lastname: Díaz-Gavilán
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-Serrano
authors.forename: Houria
authors.initials: H
authors.lastname: Boulaiz
authors.forename: Antonia
authors.initials: A
authors.lastname: Aránega
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gallo
authors.forename: Juan A
authors.initials: JA
authors.lastname: Marchal
authors.forename: Joaquín M
authors.initials: JM
authors.lastname: Campos
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D020411:Oligonucleotide Array Sequence Analysis; D011687:Purines / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018076:DNA, Complementary; D011687:Purines