RESUMEN
Eighteen uronic acid derivatives were designed and synthesized, and the cytotoxicities in vitro of two cancer cell lines (BEL7402 and SGC7901) were evaluated by MTT assay. The results showed that the inhibitory rate of the compounds on both cell lines was significantly higher than the parent compound. The IC50 of compounds II4, II6, III4, and III6 are comparable or stronger than the positive control drug, the interactions between compounds II4, II6, III4, III6, and NF-κB were also studied by docking simulations.
Asunto(s)
Antineoplásicos , Línea Celular Tumoral , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-Actividad , Triterpenos , Ácido UrsólicoRESUMEN
Based on the simulation of the docking of survivin protein with known small molecule inhibitors, the active groups which can bind to target proteins were analyzed by the techniques of computer-aided drug design (CADD). These active groups were introduced into the A-ring of asiatic acid and their C-28 sites were reconstructed simultaneously. Ten asiatic acid derivatives were designed and synthesized, and their structures were confirmed by MS and NMR. The inhibitory activities of the asiatic acid derivatives against HepG2 and SGC7901 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The results showed that compounds I6 and II4 exhibited more potent cytotoxicity than the positive control drug gefitinib, which was comparable to that of adriamycin.[Formula: see text].
