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
| Autor: | Joaquín M. Campos, Juan A. Marchal, Mónica Díaz-Gavilán, Fernando Rodríguez-Serrano, Antonia Aránega, Octavio Caba, Houria Boulaiz, Miguel A. Gallo |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Purine
DNA Complementary Population Cell Gene Expression Antineoplastic Agents Apoptosis Inhibitory Concentration 50 chemistry.chemical_compound Cell Line Tumor Complementary DNA Drug Discovery medicine Humans education Purine metabolism Oligonucleotide Array Sequence Analysis Pharmacology education.field_of_study Chemistry Cell Cycle Organic Chemistry General Medicine Molecular biology medicine.anatomical_structure MCF-7 Purines Cell culture Drug Screening Assays Antitumor |
| Zdroj: | European Journal of Medicinal Chemistry. 46:3802-3809 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2011.05.047 |
| Popis: | Completing a SAR study, a series of ( RS )-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7 H or 9 H -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-(9 H -fluorenyl-9-methoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-6-chloro-9 H -purine ( 16 , IC 50 = 0.67 ± 0.18 μM), whilst ( RS )-7-{2-( N -hydroxymethylphenyl)-2-nitrobenzenesulfonamido]-1-methoxyethyl}-6-chloro-7 H -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. |
| Databáze: | OpenAIRE |
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