RESUMEN
A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the "tail approach" and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.
Asunto(s)
Carbohidratos/farmacología , Sulfonamidas/síntesis química , Sulfonamidas/farmacología , Tiadiazoles/síntesis química , Tiadiazoles/farmacología , Inhibidores de Anhidrasa Carbónica/síntesis química , Inhibidores de Anhidrasa Carbónica/farmacología , Anhidrasas Carbónicas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células HT29 , Humanos , Simulación del Acoplamiento Molecular , Microambiente Tumoral/efectos de los fármacosRESUMEN
A series of oleanolic acid derivatives bearing acetyl-substituted l-arabinose moiety has been synthesized and screened in vitro for cytotoxicity against ten cancer cell lines and four normal cell lines. The antiproliferative evaluation indicated that synthetic derivatives showed excellent selectivity, as they were toxic against only A431 cell line. Among them, the compound 6 possesses the best inhibitory activity. A series of pharmacology experiments showed that compound 6 significantly induced A431 cells apoptosis and cell cycle arrest, which could serve as a promising lead candidate for further study.
