RESUMO
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.
Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia/patologia , Sulfanilamidas/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Humanos , Leucemia/tratamento farmacológico , Leucemia/metabolismo , Modelos Moleculares , Estrutura Terciária de Proteína , SulfanilamidaRESUMO
IUD translocation to the sigmoid colon after uterine perforation is a rare but serious event. Removal of the IUD in such a situation has been recommended because of the risk of complication, such as fistula formation and colonic perforation. We present the case of a 43-year-old female with a copper T380A IUD embedded in the sigmoid colon, which was removed with minimally invasive techniques.
