Diterpenoids from Euphorbia peplus possessing cytotoxic and anti-inflammatory activities.

Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be ß-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ1 migrating to Δ1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC50 values within 2-5 µM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways.

Natural Enantiomers: Occurrence, Biogenesis and Biological Properties.

The knowledge that natural products (NPs) are potent and selective modulators of important biomacromolecules (e.g., DNA and proteins) has inspired some of the world's most successful pharmaceuticals and agrochemicals. Notwithstanding these successes and despite a growing number of reports on naturally occurring pairs of enantiomers, this area of NP science still remains largely unexplored, consistent with the adage "If you don't seek, you don't find". Statistically, a rapidly growing number of enantiomeric NPs have been reported in the last several years. The current review provides a comprehensive overview of recent records on natural enantiomers, with the aim of advancing awareness and providing a better understanding of the chemical diversity and biogenetic context, as well as the biological properties and therapeutic (drug discovery) potential, of enantiomeric NPs.

Bioactive sesquiterpenoids from the flower buds of Tussilago farfara.

Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of 13C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.

Thiophene enantiomers from the aerial parts of Eclipta prostrata.

Ten thiophene derivatives (1-10), including two previously undescribed ones (1 and 2), have been obtained and structurally characterized from the aerial parts of a traditional Chinese herb Eclipta prostrata. Six of them with one chiral center were identified to be scalemic mixtures, and the pure enantiomers of two isolates (1 and 3) were successfully separated via chemical derivatization and chiral HPLC, with the absolute configurations being established by analysis of optical rotations. All the thiophenes were subjected to a series of assays and compounds 9 and 10 exhibited mild antibacterial activity against Staphylococcus aureus.[Formula: see text].

Diarylheptanoids with NO production inhibitory activity from Amomum kravanh.

Seven new diarylheptanoids, kravanhols C-I (1-7), along with two known analogues (8 and 9), were isolated from the fruits of Amomum kravanh. The structures of compounds 1-7 were elucidated by analysis of spectroscopic data, and the absolute configurations of selective ones were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells. Compounds 2, 5, 6 and 9 exhibited moderate inhibitory activity with IC50 values in the range of 17.4-26.5 µM, being more potent than the positive control dexamethasone (IC50 = 32.5 µM).

Limonoids from Cipadessa baccifera.

Eighteen new limonoids, including eight methyl angolensates (1-8) and 10 cipadesins (9-18), were isolated from the leaves of Cipadessa baccifera. Their structures were characterized by means of spectroscopic data analyses, single-crystal X-ray diffraction, and quantum chemistry computational methods. The C-6 configurations in those compounds possessing a C-6 hydroxy group were all assigned as S regardless of the magnitude of J5,6, and the C-2' configuration in those bearing a 2-methylbutyryl residue was defined by single-crystal X-ray diffraction and NMR data. Compounds 1, 5, 6, 7, 11, and 12 showed moderate antimalarial activities with IC50 values ranging from 12 to 28 µM.

Structural characterization and biological evaluation of chemical constituents from Ilex cornuta.

One new ursane-type triterpenoid (1), one new ursane-type triterpenoid glycoside (2), and one new oleanane-type triterpenoid glycoside (3), along with 20 known compounds, were isolated from the leaves of Ilex cornuta. The structures of these natural products were elucidated on the basis of detailed spectroscopic analyses and chemical derivation. Our biological evaluation established that selective compounds showed moderate to significant antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods.

Two new naphthoate derivatives from Morinda officinalis.

Two new naphthoate derivatives, including a symmetrical dimer (1) and a monomer (2), were separated from the roots of Morinda officinalis var. hirsuta. Their structures were characterized on the basis of spectroscopic means especially MS and NMR methods. Biological evaluations revealed that the two compounds did not show inhibition against both cholinesterases AChE and BChE, while the dimer (1) did exhibit moderate growth inhibitory activity toward one human osteosarcoma cell line U2OS with an IC50 value of 18.5 ± 1.1 µM.

Structural Elucidation and Total Synthesis of Three 9-Norlignans from Curculigo capitulata.

Capitulactones A-C, three unprecedented 9-norlignans featuring a unique 3,5-dihydrofuro[2,3- d]oxepin-7(2 H)-one scaffold, were isolated from the roots of Curculigo capitulata. Their structures with absolute configurations were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Biomimetic total syntheses of three pairs of the corresponding enantiomers were achieved in 9-10 steps with overall yields of 14.8, 12.7, and 10.3%, respectively. Notably, the unique scaffold of the common western hemisphere of the molecules was constructed by using the oxidation-reduction strategy from benzodihydrofuran.

Germacrane-type sesquiterpenoids with cytotoxic activity from Sigesbeckia orientalis.

Eleven new highly oxygenated germacrane-type sesquiterpenoids (1-11) and 16 known analogues (12-27) were isolated from the aerial parts of Sigesbeckia orientalis. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially NMR and ECD analyses. Compounds 13, 21 and 23 possessing an 8-methacryloxy group showed stronger in vitro cytotoxicity against human A549 and MDA-MB-231 cancer cell lines than other co-metabolites, with IC50 values ranging from 6.02 to 10.77 µM comparable to the positive control adriamycin.

Chromane Enantiomers from the Flower Buds of Tussilago farfara L. and Assignments of Their Absolute Configurations.

Fourteen chromane derivatives of seven pairs of enantiomers (1-14) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α-glucosidase inhibitory activities.

Cuceolatins A-D: New Bioactive Diterpenoids from the Leaves of Cunninghamia lanceolata.

Four new diterpenoids named cuceolatins A-D, including three labdane-type (1-3) and one abietane-type (4) as well as three known labdane analogs (5-7), were reported from the leaves of Cunninghamia lanceolata. Structural assignments for these compounds were conducted by analyses of spectroscopic data, and their absolute configurations were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. Among them, the abietane-type diterpenoid (11-hydroxy-12-methoxyabieta-8,11,13-trien-3-one (4)) showed significant cytotoxicity against human MDA-MB-231, MCF-7, and HeLa tumor cell lines with IC50 measurements of 4.3, 2.8 and 4.5 µm, respectively, while the labdane-type diterpenoids with a 4α-carboxy group (1-3 and 5) exhibited moderate antibacterial activity towards Bacillus subtilis and Staphylococcus aureus with IC50 values all below 25 µm.

Acylphloroglucinols as kinase inhibitors from Sargassum nigrifoloides.

Three new acylphloroglucinols (1-3) and four known biosynthetically related analogs (4-7) were isolated from the ethanol extract of a brown alga Sargassum nigrifoloides. Structures for 1-7 were characterized via detailed spectroscopic analyses especially 2D NMR data. Screening of these compounds in Alzheimer's diseases-related bioassays revealed moderate inhibitory activities against two therapeutically important kinases, CDK5 and GSK3ß. A preliminary structure-activity relationship was also discussed.

New e:b-Friedo-Hopane Type Triterpenoids from Euphorbia peplus with Simiarendiol Possessing Significant Cytostatic Activity against HeLa Cells by Induction of Apoptosis and S/G2 Cell Cycle Arrest.

Seven rare e:b-friedo-hopane-type triterpenoids including four new (1-4) and three known (5-7) ones with 5 being first reported as a natural product, together with five other known triterpenoids (8-12), were isolated from the nonpolar fractions of the ethanolic extract of Euphorbia peplus. Structural assignments for these compounds were based on spectroscopic analyses and quantum chemical computation method. The structural variations for the C-21 isopropyl group, including dehydrogenation (1 and 3) and hydroxylation at C-22 (simiarendiol, 2), were the first cases among e:b-friedo-hopane-type triterpenoids. Simiarendiol (2) bearing a 22-OH showed significant cytostatic activity against HeLa and A549 human tumor cell lines with IC50 values of 3.93 ± 0.10 and 7.90 ± 0.31 µM, respectively. The DAPI staining and flow cytometric analysis revealed that simiarendiol (2) effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in a dose-dependent manner in HeLa cells.

Bioactive Pyridone Alkaloids from a Deep-Sea-Derived Fungus Arthrinium sp. UJNMF0008.

Eight new 4-hydroxy-2-pyridone alkaloids arthpyrones D⁻K (1⁻8), along with two known analogues apiosporamide (9) and arthpyrone B (10), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. The structures of the isolated compounds were elucidated on the basis of spectroscopic methods with that of 1 being established by chemical transformation and X-ray diffraction analysis. Compounds 1 and 2 bore an ester functionality linking the pyridone and decalin moieties first reported in this class of metabolites, while 3 and 4 incorporated a rare natural hexa- or tetrahydrobenzofuro[3,2-c]pyridin-3(2H)-one motif. Compounds 3⁻6 and 9 exhibited moderate to significant antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus with IC50 values ranging from 1.66⁻42.8 µM, while 9 displayed cytotoxicity against two human osteosarcoma cell lines (U2OS and MG63) with IC50 values of 19.3 and 11.7 µM, respectively.

New Octadecanoid Enantiomers from the Whole Plants of Plantago depressa.

In this study, 19 octadecanoid derivatives-four pairs of enantiomers (1⁻8), two racemic/scalemic mixtures (9⁻10), and nine biosynthetically related analogues-were obtained from the ethanolic extract of a Chinese medicinal plant, Plantago depressa Willd. Their structures were elucidated on the basis of detailed spectroscopic analyses, with the absolute configurations of the new compounds assigned by time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculations. Six of them (1, 3⁻6, and 9) were reported for the first time, while 2, 7, and 8 have been previously described as derivatives and are currently obtained as natural products. Our bioassays have established that selective compounds show in vitro anti-inflammatory activity by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells.

New Chromones from a Marine-Derived Fungus, Arthrinium sp., and Their Biological Activity.

Five new chromone derivatives, arthones A⁻E (1⁻5), together with eight known biogenetically related cometabolites (6⁻13), were isolated from a deep-sea-derived fungus Arthrinium sp. UJNMF0008. Their structures were assigned by detailed analyses of spectroscopic data, while the absolute configurations of 1 and 5 were established by electronic circular dichroism (ECD) calculations and that of 2 was determined by modified Mosher ester method. Compounds 3 and 8 exhibited potent antioxidant property with DPPH and ABTS radical scavenging activities, with IC50 values ranging from 16.9 to 18.7 µM. Meanwhile, no compounds indicated obvious bioactivity in our antimicrobial and anti-inflammatory assays at 50.0 µM.

Limonoids and Triterpenoids as 11ß-HSD1 Inhibitors from Walsura robusta.

Nine new cedrelone-type limonoid derivatives, walsunoids A-I (1-9), and 11 known compounds were isolated from the leaves of Walsura robusta. Walsunoid A (1) is a new degradation product of cedrelone-type limonoids, and walsunoid I (9) is a rare cedrelone-type limonoid amide. Their structures and absolute configurations were determined by spectroscopic data, single-crystal X-ray diffraction, and ECD data analyses. Five compounds showed moderate inhibitory activities against human and/or mouse 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) with IC50 values ranging from 0.69 to 9.9 µM.

Limonoids with Anti-HIV Activity from Cipadessa cinerascens.

Sixteen new limonoids, named ciparasins A-P (1-16), comprising three structural categories of trijugin-type (1-7), cipadesin-type (8-15), and prieurianin-type (16) compounds, as well as 15 known limonoid analogues (17-31), were isolated from Cipadessa cinerascens. Ciparasins E-G (5-7) were found to possess a rare γ-hydroxylbutenolide moiety at C-17. Ciparasins B (2) and P (16) showed significant anti-HIV activities, with EC50 values of 5.5 ± 0.6 (SI >7.2) and 6.1 ± 0.7 (SI >6.5) µM, respectively.

New diterpenoids from Sapium discolor.

Chemical fractionation of the ethanolic extract generated from the twigs and leaves of Sapium discolor led to the isolation and identification of four new macrocyclic diterpenoids including three members of the rare casbane family, sapidisins A-C (1-3), and an analog of the cembrane class, sapidisin D (4), a new 3,4-seco ent-kaurane diterpenoid (5), and 18 known phenolic compounds. Their structures were elucidated by comprehensive spectroscopic analyses especially 1D NMR (1)H-(1)H couplings and 2D NMR ROESY data. The discovery of 1-4 from S. discolor provides a clue for further study on the biogenetic evolution of the widely existent tigliane-type diterpenoids in the Sapium species.