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
The semisynthesis of novel derivatives of lupeyl palmitate and 3ß-palmitoyloxy-olean-12-ene by introduction of a pyrazine at C-2 / C-3 and modifications of the relatively unexplored C-30 position of lupeol derivatives was conducted, and their cytotoxic and anti-inflammatory activities were evaluated. The derivatives 7, 10 and 11 significantly inhibited the tumor cell lines U251, K562, HCT-15, MCF-7 and SKLU-1, and compounds 7 and 11 were more active (IC50 25.4 ± 2.0 µM and 7.1 ± 0.4 µM, respectively) than the positive control (etoposide (IC50 31.5 ± 2.2 µM) in the tumor line PC-3. Introduction of the pyrazine at C-2 / C-3 in compounds 1 and 2 or modification at C-30 of compound 1 decreased the anti-inflammatory activity in the TPA-induced mouse ear edema. Following the results of the PASS online evaluation of the potential biological activity of the natural compounds and their derivatives, the inhibition of pNF-κB translocation to the prostate cancer (PC-3) cell nucleus was investigated and the binding mode of compounds 7, 10 and 11 with the human NF-κB receptor was explored by a molecular docking study. These derivatives bound directly or close to the amino acids that form the DNA recognition site. The ADMET physicochemical parameters of the fifteen compounds were further analyzed in silico using Molinspiration calculations indicating the potential of compounds 7, 10 and 11 for further investigation.
Assuntos
Antineoplásicos , Triterpenos , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Triterpenos Pentacíclicos/farmacologia , Pirazinas , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologiaRESUMO
The new compound totaiol (isolated from Acrocomia totai) was misnamed as a hopane-type triterpene. Considering its biosynthesis, it could be considered as an intermediate of other triterpenes isolated from the same source (following a sterol folding of 2,3-squalene oxide). In contrast, hopane-type triterpenes follow a different biosynthetic route (non-sterol folding of 2,3-squalene oxide). The stereochemical and substitutional array trans, syn, trans, anti, trans, anti, trans for the A-E rings of the triterpene totaiol (1) is not known, and therefore, its biosynthetic significance as an important intermediate should be emphasized. This new group of triterpenic skeletons could be named totaianes.[Formula: see text].
Assuntos
Arecaceae , Triterpenos , Esqualeno , Árvores , Triterpenos/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
Chemical investigation of the aerial parts of Cnidoscolus spinosus resulted in the isolation of relatively infrequent hopane-type triterpenes, 3ß-acetoxy-hop-22(29)-ene (1), first reported here as natural product, together with 3-oxo-hop-22(29)-ene (2), and 3ß-hydroxy-hop-22(29)-ene (3). ß-Amyrin palmitate and three phytosterols were also characterized. The structures of the compounds were established using spectroscopic methods, and those of 1 and 2 were confirmed by crystallographic analysis. Selected biological activities for the isolated hopane-type triterpenes were tested through a series of assays for determining the cytotoxic, anti-inflammatory, α-glucosidase inhibition and antiparasitic activities. Compounds 1-3 did not show cytotoxic activity, compound 1 displayed an important inhibitory effect in the mouse ear induced inflammation assay, and significantly inhibited the yeast α-glucosidase activity in vitro and in silico. Additionally, compounds 2 and 3 showed marginal activities against Trypanosoma cruzi and Leishmania mexicana. Therefore, the bioactivities of hopane-type triterpenes deserve further investigation, particularly their anti-inflammatory properties.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Euphorbiaceae/química , Triterpenos/química , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antiparasitários/química , Antiparasitários/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Triterpenos/isolamento & purificação , Leveduras/enzimologia , alfa-Glucosidases/metabolismoRESUMO
The activities of 11 C-8-O-acyl and alkyl analogs of the antiprotozoal sesquiterpene lactone, incomptine A (1) against Entamoeba histolytica and Giardia lamblia, were determined. Here, the effects of different lengths and amounts of branching of the acyl and alkyl groups on the antiprotozoal activity of the synthesized incomptine A-analogs are reported.