Cytotoxicity of Novel Sulfanilamides Towards Sensitive and Multidrugresistant Leukemia Cells

Author(s): T. AlSalim, M.E.M. Saeed, J.S. Hadi, M. Zeino, R. Gany, O. Kadioglu, S.J.J. Titinchi, H.S. Abbo, T. Efferth

Journal Name: Current Medicinal Chemistry

Volume 21 , Issue 23 , 2014


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Abstract:

Novel sulfa Schiff bases were synthesized and characterized by a reaction between aromatic sulfonamides and aromatic aldehydes or heterocyclic ketones in equimolar ratios. Their cytotoxicity was evaluated by the resazurin assay towards human sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. Three of the tested compounds viz., 4-(anthracen-9-ylmethyleneamino)-N-(pyrimidin-2-yl)benzenesulfonamide (4), 4-(anthracen-9- ylmethyleneamino)benzenesulfonamide, (5) and 4-((3-phenylallylidene)amino)benzene-sulfonamide, (6) were cytotoxic (IC50 values: 5.38-19.96 µM). CEM/ADR5000 cells were not cross-resistant to these compounds, indicating activity against otherwise drug-resistant tumors. Compound 6 inhibited P-glycoprotein by increasing doxorubicin accumulation and reducing expression of P-glycoprotein in CEM/ADR5000 cells. A human P-glycoprotein homology model was used for molecular docking studies. Compound 6 and verapamil (a well-known P-glycoprotein inhibitor) docked with similar binding energies to the same binding pocket.

Keywords: Anthraldehyde, cancer, cinnamaldehyde, condensation, isatin, multidrug resistance, sulpha drugs, schiff bases.

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Article Details

VOLUME: 21
ISSUE: 23
Year: 2014
Published on: 20 January, 2014
Page: [2715 - 2725]
Pages: 11
DOI: 10.2174/0929867321666140120120708
Price: $65

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