RESUMEN
Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.
RESUMEN
Rugosiformisin A, a skeleton-rearranged abietane-type diterpenoid with a spiro[4.5]decane motif, was isolated from Isodon rugosiformis. Its structure was unambiguously established via NMR spectroscopic analysis and single-crystal X-ray diffraction. A bioinspired asymmetric synthesis of rugosiformisin A was achieved in 15 steps with 2.7% overall yield. The synthesis features an iridium-catalyzed asymmetric polyene cyclization and a semipinacol rearrangement.
Asunto(s)
Diterpenos , Isodon , Isodon/química , Abietanos/química , Espectroscopía de Resonancia Magnética , Extractos Vegetales/química , Esqueleto , Estructura Molecular , Diterpenos/químicaRESUMEN
Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 0.6 µmol·L-1.
Asunto(s)
Antineoplásicos Fitogénicos/química , Diterpenos de Tipo Kaurano/química , Medicamentos Herbarios Chinos/química , Isodon/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Resonancia Magnética Nuclear Biomolecular , Componentes Aéreos de las Plantas/química , Células RAW 264.7RESUMEN
Seven previously undescribed 7,20-epoxy-ent-kaurane diterpenoids, isojiangrubesins A-G, along with seventeen known ones, were isolated from the aerial parts of Isodon rubescens. Their structures were characterized on the basis of spectroscopic methods and signal-crystal X-ray diffraction. All of these compounds were evaluated for their in vitro cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480). Four isolates exhibited significant inhibitory ability against all cell lines, with IC50 values ranging from 0.5 to 6.5 µM; They also strongly inhibited NO production in LPS-stimulated RAW264.7 cells.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Isodon/química , Antineoplásicos Fitogénicos/química , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Células HL-60 , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Estructura Molecular , Óxido Nítrico/biosíntesis , Componentes Aéreos de las Plantas/químicaRESUMEN
Fourteen new diterpenoids (1-14) based on four skeletal types and two known analogues (15 and 16) were isolated from the aerial parts of Isodon scoparius. Compound 2 is the first ent-kaurane diterpenoid featuring a 1,11-ether bridge, and the structures of these new compounds were established mainly by NMR and MS methods. The absolute configurations of 1 and 5 and the relative configuration of 3 were determined using single-crystal X-ray diffraction. The absolute configuration of 14 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 4, and 15 were active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and they also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 1.0, 3.1, and 1.8 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon/química , Componentes Aéreos de las Plantas/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Estructura Molecular , Óxido Nítrico/biosíntesis , Resonancia Magnética Nuclear BiomolecularRESUMEN
Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14ß)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 µM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480).
Asunto(s)
Abietanos/química , Abietanos/aislamiento & purificación , Isodon/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Abietanos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular , Línea Celular Tumoral , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Óxido Nítrico/biosíntesis , Componentes Aéreos de las Plantas/química , Extractos Vegetales/farmacologíaRESUMEN
Nine 7,20-epoxy-ent-kaurane diterpenoids (15-acetylmegathyrin B, serrin E, 14ß-hydroxyrabdocoestin A, serrin F, serrin G, 11-epi-rabdocoestin A, serrin H, serrin I, and 15-acetylenanderianin N), along with seven known ones, were isolated from the aerial parts of Isodon serra. Their structures were elucidated by extensive spectroscopic analysis, and the absolute configuration of 15-acetylmegathyrin B was determined by signal-crystal X-ray diffraction. All of these compounds were evaluated for their cytotoxic activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480). Serrin F, rabdocoestin B and 1α,11ß-dihydroxy-1α,11ß-acetonide-7α,20-epoxy-ent-kaur-16-en-15-one showed cytotoxic activities against all cell lines, with IC50 values ranging from 0.7 to 4.6 µM; serrin F also strongly inhibited NO production in LPS-stimulated RAW264.7 cells. Otherwise, 14ß-hydroxyrabdocoestin A, serrins H and I, as well as enanderianin N and megathyrin B, also exhibited inhibitory effects towards NO production, while no cytotoxicity against five cell lines was detected.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Isodon/química , Animales , Antineoplásicos Fitogénicos/química , Diterpenos de Tipo Kaurano/química , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/biosíntesis , Componentes Aéreos de las Plantas/químicaRESUMEN
Seven new ent-kaurane diterpenoids, isowikstroemins A-G (1-7), were isolated from EtOAc extracts of the aerial parts of Isodon wikstroemioides. Their structures were elucidated by extensive spectroscopic analysis. The isolates were evaluated for their cytotoxicity against five human tumor cell lines, and compounds 1-4 exhibited significant activity with IC50 values ranging from 0.9 to 7.0 µM. In addition, compounds 1, 2, 3, 4, and 7 exhibited inhibitory activity against nitric oxide (NO) production in LPS-activated RAW264.7 macrophages.
Asunto(s)
Antineoplásicos Fitogénicos/química , Diterpenos de Tipo Kaurano/química , Isodon/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Componentes Aéreos de las Plantas/químicaRESUMEN
Phytochemical investigation of EtOAc extracts of the aerial parts of Isodon wikstroemioides afforded 18 new ent-kaurane diterpenoids (wikstroemioidins E-V, 1-18), along with 17 known analogues (19-35). The absolute configurations of 1 and 16 were confirmed by single-crystal X-ray diffraction analysis. The isolates were screened against five human tumor cell lines; compounds 3, 4, 9, 11-13, 23, 25-28, and 33 exhibited significant cytotoxic activity against all five, with IC50 values ranging from 0.4 to 5.1 µM. In addition, 17 of the isolates strongly inhibited nitric oxide production in LPS-activated RAW264.7 macrophages.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Medicamentos Herbarios Chinos , Isodon/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Cristalografía por Rayos X , Diterpenos de Tipo Kaurano/química , Diterpenos de Tipo Kaurano/aislamiento & purificación , Diterpenos de Tipo Kaurano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/biosíntesis , Resonancia Magnética Nuclear BiomolecularRESUMEN
Phytochemical investigation of the aerial parts of Isodon sculponeatus afforded six new 7,20-epoxy-ent-kauranoids, sculponins U-Z (1-6), and 11 known diterpenoids (7-17). The structures of these new compounds were elucidated primarily by means of extensive spectroscopic analysis, and the absolute configuration of 1 was determined by single crystal X-ray diffraction. Compound 5 exhibited weak cytotoxic activity against HL-60, SMMC-7721, MCF-7, and SW-480 cell lines, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 value of 13.8 µM.
Asunto(s)
Diterpenos/aislamiento & purificación , Isodon/química , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Células MCF-7 , Estructura Molecular , Plantas Medicinales/químicaRESUMEN
Fourteen enmein-type 6,7-seco-ent-kaurane diterpenoids, seven new ones (sculponins M-S, 1-7) and seven known compounds (8-14), were isolated from the aerial parts of Isodon sculponeatus . Compound 1 is the first example of an ent-kauranoid, possessing a 11,12-epoxy group, and compounds 6 and 7 have a rare 3,6-epoxy group. The structures were established primarily by NMR and MS methods, and the absolute configurations of 1, 3, and 6 were determined by single-crystal X-ray diffraction. Compound 14 showed significant cytotoxic activity against five human tumor lines, with IC50 values ranging from 1.0 to 3.5 µM, and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 2.2 µM.