6533b82efe1ef96bd1293407

RESEARCH PRODUCT

Cytotoxicity of Novel Sulfanilamides Towards Sensitive and Multidrugresistant Leukemia Cells

R. GanyJabbar S. HadiMaen ZeinoSalam J.j. TitinchiMohamed E.m. SaeedHanna S. AbboThomas EfferthTahseen A. AlsalimOnat Kadioglu

subject

Models MolecularCell SurvivalStereochemistryBiochemistrychemistry.chemical_compoundSulfanilamideCell Line TumorSulfanilamidesDrug DiscoverymedicineHumansCytotoxic T cellDoxorubicinATP Binding Cassette Transporter Subfamily B Member 1Homology modelingCytotoxicityPharmacologyLeukemiaChemistryOrganic ChemistryResazurinSulfanilamidemedicine.diseaseProtein Structure TertiaryLeukemiaDoxorubicinDrug Resistance NeoplasmMolecular MedicineVerapamilmedicine.drug

description

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 (IC 50 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.

yearjournalcountryeditionlanguage
2014-01-20Current Medicinal Chemistry
https://doi.org/10.2174/0929867321666140120120708