Identification of cytotoxic, T-cell-selective 1,4-benzodiazepine-2,5-diones
| Autor: | Gary D. Glick, Thomas B. Sundberg, Tasha M. Francis, Joanne Cleary, Anthony W. Opipari, Groendyke Todd Michael |
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| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
medicine.drug_class Stereochemistry ATPase T-Lymphocytes Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Mitochondrion Biochemistry Benzodiazepines Jurkat Cells Structure-Activity Relationship Drug Discovery medicine Potency Humans Cytotoxic T cell Moiety Cytotoxicity Molecular Biology Benzodiazepine B-Lymphocytes biology Cell Death Molecular Structure Chemistry Organic Chemistry Stereoisomerism General Medicine Mechanism of action Apoptosis Cell culture biology.protein Molecular Medicine medicine.symptom |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 16:2423-2427 |
| ISSN: | 0960-894X |
| Popis: | A family of 1,4-benzodiazepine-2,5-diones (BZDs) has been synthesized and evaluated against transformed B- and T-cells for lymphotoxic members. A large aromatic group on the C3 position is critical for cytotoxicity. When the C3 moiety contains an electron-rich heterocycle, the resulting BZDs have sub-micromolar potency and are selective for T-cells. Cell death is consistent with apoptosis and does not result from inhibition of the mitochondrial F o F 1 -ATPase, which is the molecular target of recently reported cytotoxic 1,4-benzodiazepines. Collectively, these studies begin to characterize some of the structural elements required for the activity of a novel family of T-cell-selective lymphotoxic agents. |
| Databáze: | OpenAIRE |
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