Neo-clerodane diterpenes from Salvia herbacea

Chemical investigation of the aerial parts of Salvia herbacea led to the isolation of eight new neo-clerodane diterpenes (1-8), named tehuanins A-H, and three known compounds. The structures of these compounds were determined by analysis of their spectroscopic data. Three of the new diterpenes possess a 1,8-epoxy group (1-3). This unusual structural feature was confirmed by X-ray diffraction of 1. The structure of the previously isolated 1α,10α-epoxysalviarin was revised. The absolute configuration of 6 was established by X-ray diffraction analysis of its bromo derivative 6a. Cytotoxic and anti-inflammatory activities of these diterpenes were examined. None of the compounds were considered to be cytotoxic; however, compound 7 exhibited anti-inflammatory activity comparable to that of indomethacin.     

Bioactive diterpenes from Callicarpa longissima

Investigation of the leaves and twigs of Callicarpa longissima resulted in the isolation of four new compounds (1-4), callilongisins A-D, and five known compounds, ursolic acid, 3-oxoanticopalic acid, (E)-6β-hydroxylabda-8(17),13-dien-15-oic acid, 5-hydroxy-3,6,7,4'-tetramethoxyflavone, and artemetin. Compounds 1-3 are 3,4-seco-abietane-type diterpenoids, and compound 4 is an analogue of a labdenoic-type diterpene. The structure of compound 1 was confirmed by X-ray crystallographic analysis. Cytotoxicity against a human prostate cancer cell line (PC3) and anti-inflammatory activities of the isolated compounds were evaluated.     

Nitric oxide inhibitory isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia

A methanolic extract of Orthosiphon stamineus yielded six new highly oxygenated isopimarane-type diterpenes, orthosiphols U-Z (1-6), and 15 previously reported diterpenes. The isolated diterpenes all showed significant dose-dependent inhibitory effects on the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Orthosiphols A (7), B (8), D (9), and X (4) showed more potent inhibitory activities than a positive control, N(G)-monomethyl-l-arginine (l-NMMA), and 1 displayed the strongest activity with an IC(50) value of 6.4 microM.     

Five novel highly oxygenated diterpenes of Orthosiphon stamineus from Myanmar

Five novel highly oxygenated diterpenes, orthosiphols K (1), L (2), M (3), and N (4) and norstaminone A (5), were isolated from the aerial part of Orthosiphon stamineus, together with three known diterpenes, orthosiphols A (6) and B (7) and neoorthosiphol A (8). Orthosiphol L (2) is an isopimarane-type diterpene with a hydroxyl group at C-12, which supports the biogenesis of staminane-type diterpenes, i.e., migration of a vinylic group from C-13 of isopimarane to C-12. Norstaminone A (5) has a staminane carbon framework and supports the biosynthetic pathway from staminols to norstaminols via staminolactones. All the isolated compounds showed mild to weak antiproliferative activities toward highly liver metastatic colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines.     

Bioactive triterpenoids from Salvia species

Salvia species are important medicinal and culinary plants, and they have been the subject of numerous chemical and biological studies. The bioactive triterpenoids of Salvia species, reported in the literature to date, are reviewed. About 200 triterpenoids, almost 80 of which are new, isolated, and characterized from about 100 Salvia species, are presented herein. In addition to the diverse biological activities of the pure triterpenoids, studies on biological activity of extracts of Salvia species are also described.     

Analgesic and antipyretic effects of Dodonaea angustifolia and Salvia africana-lutea

Water extracts of Dodonaea angustifolia L. and Salvia africana-lutea L., were investigated for analgesic and antipyretic activities using acetic acid writhing and hot plate tests, and lipopolysaccharide (LP)-induced pyrexia test in mice and rats, respectively. D. angustifolia and S. africana-lutea significantly inhibited acetic acid-induced writhing and also significantly delayed the time of reaction of mice to thermal stimulation produced by the hot plate. D. angustifolia and S. africana-lutea significantly reduced fever induced by LP. Paracetamol produced similar effects to D. angustifolia and S. africana-lutea on the acetic acid-induced writhing but has no effect on hot plate-induced nociception and on pyrexia produced by LP. These data indicate the analgesic and antipyretic potential of D. angustifolia and S. africana-lutea.     

Bioactive diterpenes from the fruits of Detarium microcarpum

A fruit pulp extract of Detarium microcarpum showed inhibition of the growth of the plant pathogenic fungus Cladosporium cucumerinum and of the enzyme acetylcholinesterase, implicated in Alzheimer's disease. Fractionation of this extract led to the isolation of four new clerodane diterpenes, 3,4-epoxyclerodan-13E-en-15-oic acid (1), 5alpha,8alpha(2-oxokolavenic acid) (2), 3,4-dihydroxyclerodan-13E-en-15-oic acid (4), and 3,4-dihydroxyclerodan-13Z-en-15-oic acid (5). Also isolated were 2-oxokolavenic acid (3) and copalic acid (6). Structure elucidation of the compounds was carried out by spectroscopic data interpretation and by the X-ray crystallography of 2 and 4. Three of the new clerodane diterpenes (1, 2, and 5) showed both antifungal activity and inhibition of acetylcholinesterase, and 3 showed a slight inhibition of this enzyme.     

Neo-clerodane diterpenes from the hallucinogenic sage Salvia divinorum

Seven new neo-clerodane diterpenes, salvidivins A (2), B, (3), C (4), and D (5), salvinorins H (6) and I (7), and divinatorin [corrected] F (8), along with eight known neo-clerodane diterpenes, salvinorins A (1)-F, divinatorins A and B, and seven other constituents, were isolated from the hallucinogenic sage Salvia divinorum. The structures of 1-7 were elucidated on the basis of 2D NMR spectroscopic studies.     

Amphilectane diterpenes from Salvia sclarea: biosynthetic considerations

Salviatrienes A and B, two new diterpenes belonging to the amphilectane/elisabethane family, have been isolated from an extract of clary sage (Salvia sclarea). These molecules are the first representatives of this family to be described from the plant kingdom. This study has led to consideration of the possible enzymatic machinery and biosynthesis pathways within S. sclarea.     

Bioactive Diterpenoids Isolated from Salvia mellifera

Eight diterpenoids were isolated from the roots of Salvia mellifera Greene. Their structures were elucidated by comparison to their physical and spectroscopy data with those reported in the literature or that of authentic samples as: abieta-8,11,13-triene, ferruginol, 15-deoxi-fuerstione, taxodione, isotanishinone III, rolyeanone, 7αsl-hydroxi-rolyleanone and demethylsalvicanol. Demethylsalvican-11-12-dione was obtained by oxidation with Ag₂O from demethylsalvicanol. Compounds ferruginol, taxodione, isotanshinone III, and 7αsl-hydroxi-royleanone showed cytotoxic activity against both HeLa and Hep-2 cells in culture. Royleanone and demethylsalvican-11-12-dione were active on Hep-2 and HeLa cells respectively. Antimicrobial activity against some Gram (+) bacteria was observed for the diterpenoids ferruginol, taxodione, 7α-hydroxi-royleanone and demethylsalvican-11-12-dione. None of them was active on Gram (−) bacteria or Candida albicans.     

Antibacterial diterpenes from the roots of Salvia blepharochlaena

The roots of Salvia blepharochlaena have yielded two new diterpenoids, blephaein (1) and O-methylpisiferic acid methyl ester (2), together with eight known diterpenoids. The structures of the new compounds were established by spectroscopic analysis and by some chemical reactions. Potent antibacterial activity was exhibited by the known compounds horminone (9) and 7-acetylhorminone (10) against Staphylococcus aureus ATCC 6538 P, Staphylococcus epidermidis ATCC 12226, and Bacillus subtilis ATCC 6633. Horminone was also found to be active against Enterococcus faecalis ATCC 29212.     

Bioactive abietane and seco-abietane diterpenoids from Salvia prionitis

From the roots of Salvia prionitis a new tricyclic diterpene, saprirearine (1), a new anhydride-type compound, saprionide (2), a new 7,8-seco-abietane diterpene derivative, 7,8-seco-para-ferruginone (3), and two new 4,5-seco-5,10-friedo-abietane diterpenoids, 4-hydroxysaprorthoquinone (4) and 3-keto-4-hydroxysaprorthoquinone (5), were isolated. Their structures were established by spectroscopic methods and chemical transformation. Compound 3 showed antimicrobial activities against two Gram-positive organisms, Staphylococcus aureus and Micrococcus luteus, with MIC values of 20.0 and 15.0 microM, respectively. Compound 4 showed significant inhibition against topoisomerase Iota with an IC50 value of 0.8 microM. Compound 5 exhibited cytotoxic activities against HL-60 human leukemia and the SGC-7901 and MKN-28 stomach cancer cell lines, with IC50 values of 4.6, 0.2, and 0.3 microM, respectively.     

Staminane- and isopimarane-type diterpenes from Orthosiphon stamineus of Taiwan and their nitric oxide inhibitory activity

From the MeOH extract of Taiwanese Orthosiphon stamineus, two new staminane-type diterpenes, staminols C (1) and D (2), and three new isopimarane-type diterpenes, orthosiphonone C (3) and D (4) and 14-deoxo-14-O-acetylorthosiphol Y (5), have been isolated together with 16 known diterpenes, orthosiphols A, B, D, K, M, N, O, X, and Y, nororthosiphonolide A, neoorthosiphol B, orthosiphonone A, secoorthosiphols B and C, 3-O-deacetylorthosiphol I, and 2-O-deacetylorthosiphol J. Their structures were determined on the basis of the spectroscopic data. All the newly isolated diterpenes exhibited dose-dependent inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells, and 2-O-deacetylorthosiphonone A showed the most potent activity, with an IC(50) value of 35.0 microM, comparable to that of the positive control N(G)-monomethyl-L-arginine (L-NMMA; IC(50), 35.7 microM).     

Bioactive diterpenes and other constituents of Croton steenkampianus

A new indanone derivative (1) and two new diterpenoids (2 and 3), together with three known flavonoids, have been isolated from an ethanol extract of the leaves of Croton steenkampianus. The structure of 2 was solved by single-crystal X-ray diffraction analysis, whereas those of 1 and 3 were established mainly by 1D and 2D NMR spectroscopic methods. The isolated compounds were tested for their antiplasmodial activity and cytotoxicity. Antiplasmodial assays against chloroquine-susceptible strains (D10 and D6) and the chloroquine-resistant strains (Dd2 and W2) of Plasmodium falciparum showed that compound 2 gave moderate activities at 9.1-15.8 μM, while none of the compounds were cytotoxic against Vero cells.     

Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge

Danshen (Salvia miltiorrhiza) is a well‐known medicinal herb in the oriental medicine. The current study on bioactive triterpenoid in the root of S. miltiorrhiza led to the isolation of a new highly hydroxylated ursane‐type triterpene, urs‐12‐ene‐2α,3β,7β,16α‐tetraol (1) and five known ones including 2β‐hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4), ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. The antiproliferative testing against HL‐60 cells revealed that the new compound 1 and ursolic acid (5) showed weak and moderate activities with IC₅₀ values of 42.2 and 11.7 μM. In addition, compounds 1–3 showed inhibitory effect on ghrelin activity. Copyright © 2017 John Wiley & Sons, Ltd.     

Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1

The hypoxia-inducible factor-1 (HIF-1) has been known to be correlated to the adaptation and proliferation of tumor cells; therefore HIF-1 has become an important target in the development of anticancer drugs. A phytochemical study of the CHCl3-soluble fraction of Salvia miltiorrhiza, which strongly inhibited hypoxia-induced reporter gene expression, led to the isolation of 12 abietane-type diterpenes. Of these compounds, sibiriquinone A (1), sibiriquinone B (2), cryptotanshinone (3), and dihydrotanshinone I (4) potently inhibited hypoxia-induced luciferase expression with IC50 values of 0.34, 3.36, 1.58, and 2.05 microM on AGS cells, a human gastric cancer cell line, and 0.28, 3.18, 1.36, and 2.29 microM on Hep3B cells, a human hepatocarcinoma cell line, respectively. Consistently, 1 and 4 dose-dependently suppressed the HIF-1alpha accumulation and 1 inhibited mRNA expression of vascular endothelial growth factor (VEGF) under hypoxia. These results suggest that the anticancer activity of tanshinones is likely at least in part associated with their inhibition of HIF-1 accumulation.     

Bioactive brominated diterpenes from the marine red alga Jania Rubens (L.) Lamx

Seven brominated diterpenes of the parguerene and isoparguerene series were isolated for the first time from the red alga Jania rubens (L.) Lamx., collected from the Red Sea coast at Hurghada, Egypt. The diterpenes were identified as isoparguerol (1), isoparguerol-16-acetate (2), isoparguerol-7,16-diacetate (3), parguerol-16-acetate (4), parguerol-7,16-diacetate (5), deoxyparguerol (6) and deoxyparguerol-7-acetate (7).The isolated diterpenes had a marked antitumour activity. Isoparguerol derivatives were slightly more effective than parguerol derivatives. Moreover, the data implied that the cytotoxicity of these compounds were dependent on the number of acetoxy groups. Also, anthelmintic activities of the isolated compounds on earthworms (Allolobophora caliginosa) were studied.     

Bioactive compounds from the gorgonian Briareum polyanthes. Correction of the structures of four asbestinane-type diterpenes

Our extended chemical investigation of the crude MeOH-CHCl3 extract of the gorgonian octocoral Briareum polyanthes from Puerto Rico has led to the isolation of three eunicellin-type diterpenoids, 1-3, along with five (4-8) diterpenoids of the asbestinane-type and one (9) of the briarane-type of polycyclized diterpenes. The structures and relative stereochemistry of the new compounds 1-9 were established on the basis of spectroscopic analysis (1H NMR, 13C NMR, HMQC, HMBC, NOESY). The biological activity of these compounds against pathogenic microbes responsible for various human infectious diseases was investigated. In addition, new data recorded for four known asbestinin diterpenes also isolated during this investigation and further analysis through chemical reactions have prompted us to revise our original structural assignments for these compounds.     

Antidiabetic Properties and Mechanism of Action of Orthosiphon stamineus Benth Bioactive Sub-fraction in Streptozotocin-induced Diabetic Rats

Orthosiphon stamineus is a popular folk medicine widely used to treat many diseases including diabetes. Previous studies have shown that the sub-fraction of chloroform extract was able to inhibit the rise of blood glucose levels in a glucose tolerance test. This study was carried out to evaluate the chronic effect and possible mechanism of action of the bioactive chloroform sub-fraction of O. stamineus using streptozotocin-induced diabetic rats and in vitro methods. Administration of the chloroform extract sub-fraction 2 (C?2-b) at a dose of 1 g/kg twice daily on diabetic rats for 14 days showed a significant lowering (p < 0.05) of the final blood glucose level compared to the pretreatment level. However, there were no significant differences in the plasma insulin levels post-treatment compared to the pretreatment levels for all doses of C?2-b. Conversely, C?2-b at a concentration of 2 mg/mL significantly increased (p < 0.001) the glucose uptake by the rat diaphragm muscle. The increase in glucose uptake was also shown when the muscle was incubated in a solution containing 1 IU/mL of insulin or 1 mg/mL of metformin. Furthermore, the effect of this sub-fraction on glucose absorption in the everted rat jejunum showed that C?2-b at concentrations of 0.5 mg/mL, 1 mg/mL and, 2 mg/mL significantly reduced the glucose absorption of the jejunum (p < 0.05–0.001). Similarly, the absorption of glucose was also inhibited by 1 mg/mL and 2 mg/mL of metformin (p < 0.001). These results suggest that the effect of C?2-b may be due to extra-pancreatic mechanisms. There was no evidence that the plant extract stimulated the release of insulin in order to lower the blood glucose level.     

Semisynthesis of rosmanol and its derivatives. Easy access to abietatriene diterpenes isolated from the genus Salvia with biological activities

The known diterpenes rosmanol (3), rosmaquinone (4), 7-methoxyrosmanol (5), 7-ethoxyrosmanol (6), galdosol (7), and epirosmanol (8) have been obtained by partial synthesis from carnosol (2), an abundant natural product present in Salvia species. The physical and spectroscopic data of these semisynthetic diterpenes were identical to those of authentic natural samples and with data reported in the literature. These abietane diterpenes have very interesting biological activities and are present in the genus Salviain low quantities; thus, the semisynthetic approach described here represents an efficient alternative method to obtain these compounds. Additionally, the known diterpene 16-hydroxyrosmanol (10) and a new aromatic diterpene 11 were obtained from 16-hydroxycarnosol (9) by reaction with Ph3P/NBS in CH2Cl2. The structure of the new compound 11 was established from its spectroscopic data as 12,16-epoxycarnosol.