Antimalarial and neuroprotective ent-abietane diterpenoids from the aerial parts of Phlogacanthus curviflorus.

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the ß-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC50 values of 12.97-65.01 µmol·L-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H2O2 and MPP+.

Antimicrobial ent-abietane diterpenoids from the leaves of Croton cascarilloide.

Three new ent-abietane diterpenoids, 6ß-hydroxy-ent-abieta-7,13-dien-3-one (1), 2ß,13α,15-trihydroxy-ent-abieta-8(14)-en-3-one (2), and 2ß,9α,13ß,15-tetrahydroxy-ent-abieta-7-en-3-one (3), were isolated from 90% ethanol extract of the leaves of Croton cascarilloide. Their structures were determined by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, NOESY, and HMBC) NMR spectroscopy, in addition to electronic circular dichroism (ECD) spectra. The isolated diterpenoids were tested in vitro for antimicrobial activity against 6 pathogenic microorganisms. As a result, compounds 1-3 exhibited antimicrobial activity against the tested Gram positive bacteria with minimum inhibitory concentration values less than 50 µg/ml.

Cytotoxic ent-abietane diterpenoids from the leaves of Croton lachnocarpus Benth.

A phytochemical investigation on the 90% ethanol extract of the leaves of Croton lachnocarpus Benth. led to three new ent-abietane diterpenoids, 7ß,15-dihydroxy-ent-abieta-8,11,13-trien-3-one (1), 2ß,15-dihydroxy-ent-abieta-8,11,13-triene (2), and 7ß,13α,15-trihydroxy-ent-abieta-8(14)-en-3-one (3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, NOESY and HMBC) NMR spectroscopy, in addition to electronic circular dichroism (ECD) spectra. The isolated compounds were tested in vitro for cytotoxic activity against 6 tumor cell lines. As a result, compound 3 exhibited some cytotoxicities against all the tested tumor cell lines with IC50 value less than 30 µM.

Diterpenoids with anti-inflammatory activity from Euphorbia wallichii.

The Euphorbia plants are the focus of natural product drug discovery because of their fascinating structural diversity and broad biological activities. Here we reported the discovery of eight undescribed diterpenoids, including two ent-trachylobanes, five ent-atisanes, and one ent-abietane, together with 15 known ones from the whole plant of Euphorbia wallichii. Their chemical structures were elucidated by detailed spectrometry data analysis and X-ray crystallography. Among them, wallichane G represents a rare ent-atisane type pentacyclic diterpenoid featuring a tetrahydrofuran moiety. Furthermore, bioassays indicated that jolkinolide B exhibited potent inhibitory activities on the production of NO, with an IC50 value of 3.84 ± 0.25 µM. Meanwhile, the mechanistic study revealed that jolkinolide B could obviously downregulate the expression of iNOS, COX-2, NF-κB, and phosphorylated IκBα in a dose-dependent manner and strongly upregulate the expression of Nrf2 and HO-1 protein, thereby suppressing the inflammatory process in macrophage cells induced by LPS.

Antimalarial and neuroprotective ent-abietane diterpenoids from the aerial parts of Phlogacanthus curviflorus / 中国天然药物

Six new ent-abietane diterpenoids, abientaphlogatones A-F (1-6), along with two undescribed ent-abietane diterpenoid glucosides, abientaphlogasides A-B (7-8) and four known analogs were isolated from the aerial parts ofPhlogacanthus curviflorus (P. curviflorus). The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) spectra, and quantum chemical calculations. Notably, compounds 5 and 6 represented the first reported instances of ent-norabietane diterpenoids from the genus Phlogacanthus. In the β-hematin formation inhibition assay, compounds 2, 4, 7-10, and 12 displayed antimalarial activity, with IC50 values of 12.97-65.01 μmol·L-1. Furthermore, compounds 4, 5, 8, and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H2O2 and MPP+.

Chemical Composition, Anti-Breast Cancer Activity and Extraction Techniques of Ent-Abietane Diterpenoids from Euphorbia fischeriana Steud.

Ent-abietane diterpenoids are the main active constituents of Euphorbia fischeriana. In the continuing search for new anti-breast cancer drugs, 11 ent-abietane diterpenoids (1-11) were isolated from E. fischeriana. The structures of these compounds were clearly elucidated on the basis of 1D and 2D NMR spectra as well as HRESIMS data. Among them, compound 1 was a novel compound, compound 10 was isolated from Euphorbia genus for the first time, compound 11 was firstly discovered from E. fischeriana. These compounds exhibited varying degrees of growth inhibition against the MCF-10A, MCF-7, ZR-75-1 and MDA-MB-231 cell lines in vitro. The experimental data obtained permit us to identify the roles of the epoxy group, hydroxyl group and acetoxyl group on their cytotoxic activities. Extraction is an important means for the isolation, identification, and application of valuable compounds from natural plants. To maximize yields of ent-abietane diterpenoids of E. fischeriana, 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A were selected as quality controls to optimize the salting-out-assisted liquid-liquid extraction (SALLE) by response surface methodology (RSM). The optimized conditions for SALLE were 0.47 g sodium dihydrogen phosphate, 5.5 mL acetonitrile and 4.5 mL water at pH 7.5. The experimental values of 17-hydroxyjolkinolide B, jolkinolide B, 17-hydroxyjolkinolide A and jolkinolide A (2.134, 0.529, 0.396, and 0.148 mg/g, respectively) were in agreement with the predicted values, thus demonstrating the appropriateness of the model.

Three new diterpenoids from Euphorbia peplus.

Three new diterpenoids (1-3) (two abietane type diterpenoids and a paralianone type diterpenoid), together with four known compounds (4-7) were isolated from the whole plants of Euphorbia peplus. Their structures were elucidated through spectroscopic analysis and physicochemical characteristics. The cytotoxic activities of compounds 1-7 against five human tumour cell lines were evaluated, however, they were inactive at the concentration of 40 µM. The compound 3 enhanced lysosomal biogenesis with Lyso Tracker staining intensity of 132.6%.

Two new ent-abietane diterpenoids from Euphorbia helioscopia.

Two new ent-abietane diterpenoids, euphcopenoids A (1) and B (2), along with six known analogues (3 - 8), were isolated from the whole plants of Euphorbia helioscopia. Their structures were determined by various spectroscopic methods (MS, UV, IR, and NMR), and the absolute configurations of compounds 1 and 2 were determined by quantum chemical ECD calculations. All compounds were screened for the cytotoxicity against A549 and HEPG2 cancer cell lines, but were inactive.[Formula: see text].

Three new ent-abietane diterpenoids from the roots of Euphorbia fischeriana and their cytotoxicity in human tumor cell lines.

Three new ent-abietane diterpenoids, termed fischerianoids A-C (1-3), were isolated and identified from the ethyl acetate extracts of roots of the medicinally valuable plant Euphorbia fischeriana. The planar and relative structures of 1-3 were established via high-resolution electrospray ionisation mass spectrometry and one- and two-dimensional nuclear magnetic resonance spectroscopic analyses, and the absolute configuration of 1 was further established via X-ray crystallography experiment. Compounds 1-3 showed selective inhibitory potency against certain human tumor cell lines with IC50 values ranging from 8.50 ± 0.13 to 35.52 ± 0.08 µM.

Isoforrethins A-D, four ent-abietane diterpenoids from Isodon forrestii var. forrestii.

Four new ent-abietane diterpenoids, isoforrethins A-D (1-4), were isolated from the aerial parts of Isodon forrestii var. forrestii by a variety of chromatographic techniques. Their structures were elucidated on the basis of spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation. All of these compounds were evaluated for their cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and compound 4 showed significant inhibitory activities against SMMC-7721, A-549, MCF-7, and SW-480.

Ent-Abietanoids Isolated from Isodon serra.

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).

ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88µM, respectively. A primary structure-activity relationship was also discussed.