RESUMO
From the bioactive extract of the euphorbiaceous Croton niveus Jacq., three previously unreported ent-rosane diterpenes have been isolated and characterized by conventional methods, in addition to the known compounds lupeol, cajucarinolide and some phytosterols. Two of the ent-rosane diterpenes displayed activity against HCT-15 and PC-3 cancer cell lines, and the results of docking calculations of these compounds with NF-κB and STAT3 receptors agreed with the proposed mode of action of diterpenes against PC-3 cells.
Assuntos
Antineoplásicos , Croton , Diterpenos do Tipo Caurano , Diterpenos , Euphorbiaceae , Estrutura Molecular , Diterpenos/farmacologia , Antineoplásicos/farmacologiaRESUMO
Ten compounds, including a new anti-inflammatory acyl triterpene, 3ß-palmitoyloxy-1ß,11α-dihydroxy-olean-12-ene, were isolated from the bioactive organic extract prepared from the leaves of Sapium lateriflorum (syn: S. nitidum). The isolated compounds were screened for their cytotoxic activity against selected human cancer cell lines and did not display significant activity. They were also evaluated as anti-inflammatory agents in mouse models (TPA-induced edema in the ear and in a carrageenan-induced paw edema model). The results indicated that the new compound, 3ß-palmitoyloxy-1ß,11α-dihydroxy-olean-12-ene, was the compound with major anti-inflammatory activity similar to that of indomethacin, being the hydroxyl at C-11 important for the observed activity. The results of docking studies of the 3ß-palmitoyloxy esters of olean-12-ene with NF-κB and with COX-2 receptors were consistent with possible molecular mechanisms of the anti-inflammatory activity.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Ésteres/farmacologia , Sapium/química , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Edema/induzido quimicamente , Ésteres/isolamento & purificação , Humanos , México , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Folhas de Planta/químicaRESUMO
The guaianolide 8-epi-mikanokryptin (1) and the melampolide 11Hß-11,13-dihydromicrantholide (2) along with known sesquiterpene lactones (3-13) and other constituents were isolated from the aerial parts of different populations of Mikania micrantha and Mikania cordifolia collected in several states of Mexico. The relative and absolute configurations of 1 were determined by X-ray diffraction and CD analysis, respectively. Considering the (1)H and (13)C NMR chemical shift similarities and the H-H coupling constant values, a [(1)D(14), (15)D5] conformation was established for micrantholides (2, 8-13). We tested nearly all the sesquiterpene lactones for antiproliferative activity in human cancer cell lines, and they exhibited moderate activity. Additionally, in a mouse ear model of edema induced by TPA, the anti-inflammatory activities were marginal.