RESUMEN
A direct nitration of aromatic sulfonamides using sodium nitrite as the nitrating agent has been developed. The reaction shows typically mono-substitution selectivity and can be enlarged to the gram scale with good yield.
RESUMEN
Carbamate derivatives of 4ß-(1,2,3-triazol-1-yl)podophyllotoxin were synthesized by means of click chemistry, and their cytotoxicities against human cancer cell lines HL-60, A-549, HeLa, and HCT-8 were evaluated. Some compounds were more potent than the anticancer drug etoposide. 4'-O-Demethyl-4ß-[(4-hydroxymethyl)-1,2,3-triazol-1-yl]-4-deoxypodophyllotoxin cyclopentyl carbamate, the most potent compound, induced cell cycle arrest in the G2/M phase accompanied by apoptosis in A-549 cells. Furthermore, this compound inhibited the formation of microtubules in A-549 cells and caused the inhibition of DNA topoisomerase-II.
Asunto(s)
Antineoplásicos/farmacología , Carbamatos/farmacología , Podofilotoxina/análogos & derivados , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Carbamatos/síntesis química , Carbamatos/química , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Células HeLa , Humanos , Estructura Molecular , Podofilotoxina/química , Podofilotoxina/farmacología , Relación Estructura-ActividadRESUMEN
A series of dichloroplatinum(II) complexes of podophyllotoxin (PPT) were prepared, and their cytotoxicity against sensitive (A-549, HeLa, HCT-8, Hep-G2, K562) and resistant (ADM/K562) cell lines were evaluated. Complex cis-[4α-O-(2â³,3â³-diaminopropanoyl)-podophyllotoxin] dichloride platinum(II) (12) displayed most potent cytotoxicity with IC50 value in the range 0.071-2.98 µM. Complex 12 induces cell cycle arrest in the G2/M phase, and inhibits the formation of microtubules in HeLa cells. Furthermore, this complex exhibits potent DNA cleavage capabilities.
