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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