Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma
| Autor: | Henrik H. Jensen, Steffen Sinning, D. Clive Williams, Sandra A. Bright, Maja Thim Larsen, Anne Brinkø |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Programmed cell death
Imipramine Cell Survival Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents Apoptosis Pharmacology Biochemistry Desipramine Cell Line Tumor Drug Discovery medicine Humans Molecular Biology Serotonin transporter Serotonin Plasma Membrane Transport Proteins biology Cell Death Chemistry Organic Chemistry medicine.disease Burkitt Lymphoma Lymphoma Cell culture biology.protein Molecular Medicine Burkitt's lymphoma Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Bright, S A, Brinkø, A, Larsen, M T, Sinning, S, Williams, D C & Jensen, H H 2013, ' Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma ', Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 5, pp. 1220-4 . https://doi.org/10.1016/j.bmcl.2013.01.020 |
| DOI: | 10.1016/j.bmcl.2013.01.020 |
| Popis: | We here report the synthesis of ethylene glycol N-interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride. The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt’s lymphoma cell line. Basic amine analogues were found to be important for increased potency. Imipramine and desipramine were also tested for apoptotic activity and were found to be much less active than the novel dimeric compounds. Imipramine dimers were only found to be moderate inhibitors of the human serotonin transporter (hSERT) having IC50 values in the micromolar region whilst the induction of cell death occurred independently of hSERT expression. These results demonstrate the potential of newly designed and synthesised imipramines derivatives for use against malignant cells, including those resistant to standard chemotherapy. |
| Databáze: | OpenAIRE |
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