Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma.

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Bright SA, Brinko A, Larsen MT, Sinning S, Williams DC, Jensen HH

Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma.

Bioorg Med Chem Lett. 2013 Mar 1;23(5):1220-4. doi: 10.1016/j.bmcl.2013.01.020. Epub 2013 Jan 12.

PubMed ID
23385211 [ View in PubMed
]
Abstract

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 IC(50) 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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DesipramineSodium-dependent serotonin transporterIC 50 (nM)560N/AN/ADetails
ImipramineSodium-dependent serotonin transporterIC 50 (nM)29N/AN/ADetails