Selective cytostatic and cytotoxic anticancer effects of bisfunctional agents: A strategy for the design of DNA binding agents

Spychala, Jaroslaw

doi:10.1016/j.canlet.2009.02.026

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Selectivity of cytostatic drugs is very important to ensure that only malignant cells and no healthy cells are affected. Most of the conventional agents cause side effects because of their limited selectivity against cancer cells [ 31 ]. A first test to determine the selectivity of a new potential agent is to test the effect on healthy leukocytes (ex vivo).…”

Section: Resultsmentioning

confidence: 99%

Dihydroxyquingdainone Induces Apoptosis in Leukaemia and Lymphoma Cells via the Mitochondrial Pathway in a Bcl-2- and Caspase-3-Dependent Manner and Overcomes Resistance to Cytostatic Drugs In Vitro

et al. 2022

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Isatis tinctoria and its indigo dyes have already provided highly active anti-leukaemic lead compounds, with the focus mainly being on indirubin, whereas indigo itself is inactive. There are many more indigoids to find in this plant extract, for example, quingdainone, an indigoid derived from tryptanthrin. We present here a new synthesis of hitherto neglected substituted quingdainones, which is very necessary due to their poor solubility behaviour, and a structure-dependent anti-leukaemic activity study of a number of compounds. Substituted α-phenylaminoacrylic acid was synthesised by hydrogen sulfide extrusion from an analogue mercaptoacetic acid, available from the condensation of rhodanin and a substituted tryptanthrin. It is shown that just improving water solubility does not increase anti-leukaemic activity, since a quingdainone carboxylic acid is inactive compared to dihydroxyquingdainone. The most effective compound, dihydroxyquingdainone with an AC50 of 7.5 µmole, is further characterised, revealing its ability to overcome multidrug resistance in leukaemia cells (Nalm-6/BeKa) with p-glycoprotein expression.

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Section: Resultsmentioning

confidence: 99%