clerodane diterpenes

..divinorum. In particular, this work provides a semisynthesis of salvinicins A (2) and B (3) and has identified 10a as the first neoclerodane diterpene with delta opioid antagonist activity...

..acetate-soluble fraction of a methanol extract of the fruits of Casearia grewiifolia afforded eight new clerodane diterpenes, caseargrewiins E-L (1-8), and a known clerodane diterpene, esculentin B (9)...

A new clerodane diterpene, 15-hydroxy-16-acetoxy-ent-clerod-3-en-18-oic acid (1), together with three known clerodane diterpenes (2-4) and three known flavones (5-7), were isolated from the aerial parts of Baccharis gaudichaudiana...

..fractionation of the EtOAc extract of Casearia membranacea leaves and twigs afforded three new clerodane diterpenes, caseamembrins M-O (1-3), and the known rel-(2S,5R,6R,8S,9S,10R,18S,19R)-2-(2-methylbutyryloxy)-6-hydroxy-..

..The structures and relative stereochemistry of 1 and 2 were elucidated by detailed 2D NMR spectroscopic experiments, and the absolute stereochemistry of 1 was determined by X-ray crystallographic analysis...

..The absolute stereochemistry of these compounds was assigned on the basis of single-crystal X-ray crystallographic analysis of salvinicin A (4) and a 3,4-dichlorobenzoate derivative of salvinorin B...

..Compounds 1-3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8) enzymes, respectively...

..fractionation of hexane and dichloromethane extracts of the bark of Casearia grewiifolia afforded four new clerodane diterpenes, caseargrewiins A-D (1-4), and two known clerodane diterpenes, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-18,19-..

Three clerodane diterpenes were isolated and identified from leaf extract of Glossocarya calcicola...

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..Compounds 1 and 2 displayed inhibitory potential against lipoxygenase enzyme in a concentration-dependent fashion with IC(50) values of 99.6 microM and 38.3 microM, respectively...

..fractionation of an EtOAc-soluble extract of Casearia membranacea has resulted in the isolation of six new clerodane diterpenes, caseamembrins A-F (1-6), and a known compound, rel-(2S,5R,6R,8S,9S,10R,18S,19R)-diacetoxy-18,19-epoxy-6-..

In addition to casearlucin A (3), two new clerodane diterpenes, caseamembrols A (1) and B (2) have been isolated from the leaves and twigs of Casearia membranacea by bioassay-guided fractionation...

..All the compounds showed effective antifeedancy against Plutella xylostella and Spodoptera litura at 10 mug/cm(2) of leaf area...

..Neither the crude extract nor 7-9 displayed antimicrobial activity...

..The structure and the relative stereochemistry of the compounds were established on the basis of their spectroscopic properties. The absolute configuration at C-13 of 1 and 5 was determined by the PGME amide procedure...

..These observations suggest that the ketone of 2b is a key structural feature responsible for mu agonist activity...

..1-7.2 microM...

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..The structure assignments are based on (1)H and (13)C NMR spectra, 2D NMR (HMQC, HMBC, COSY, NOESY and NOE) techniques and comparison with the literature data...

..Our experiments demonstrate that the relatively well-accessible diterpenoid 6 could be used as starting material for future studies into the structure-activity relationship at the kappa-opioid receptor...

..The structures of compounds 1-4 were determined using 1D and 2D NMR spectroscopy. All four compounds showed moderate cytotoxicity to the A2780 human ovarian cancer cell line, with an IC50 range of 0.83-1.4 microM...

..5-6.7 microM...

..These results together with findings reported for DCTN in vivo, support the indication of this active principle at these concentrations for therapeutic use...

..Their structures were established based on spectroscopic data, and their antibacterial activities were evaluated (Table 2)...

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, ..

..The absolute configuration was determined by application of the modified Mosher's method and chemical transformation. The inhibitory activities of the isolated compounds against alpha-glucosidase are also described...

..intermedia. Their structures have been elucidated by detailed spectroscopic analysis. In addition, the in vitro antiplasmodial activity of four isolated compounds (cornutin C-F) has been evaluated, revealing only a marginal activity...

..o.), was more effective. The presence of a lactone moiety or Michael acceptor is probably essential for the anti-ulcerogenic effect of these compounds...

..The structures were established by the interpretation of the spectral data. All the described compounds exhibited weak antimalarial activity...

..Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported...

..tucumanensis, were isolated and bioassayed. The clerodane 1 showed higher antifeedant activity than other related compounds. Structure-activity relationships are also discussed...

..Thus, the protective and healing actions of the essential oil from C. cajucara bark on gastric lesions resulted mainly from an increase in PGE2 release and gastric mucus formation which would protect the gastric mucosa...

..Thus, aging reduced the cytotoxic effects of DHC derivatives in isolated hepatocytes, suggesting that P450-mediated biotransformation of such derivatives may lead to the formation of more toxic metabolites...

..Structures were established based on spectroscopic and X-ray analysis. Croblongifolin showed a significant cytotoxicity against various human tumor cell lines including HEP-G2, SW620, CHAGO, KATO3 and BT474...

As part of a study on antitumor agents from rainforest plants, four new clerodane diterpenes, bucidarasins A--D (1-4), were isolated from Bucida buceras. Their structures were elucidated from detailed 2D NMR analyses...

..CONCLUSION: The results suggest that t-DCTN has an antidiabetic potential that warrants further research on its mechanism and clinical significance...

..The structures of the compounds were deduced on the basis of their physical and spectral data...

..type furano diterpenoids were isolated from the aerial part of Croton schiedeanus, besides the clerodane diterpenes cis- and trans-dehydrocrotonin, previously isolated from other species of Croton...

..According to the chemical characteristics of both compounds, the cytotoxic effect of t-DCTN could be explained through two mechanisms: adduct formation with DNA and proteins and/or oxidative stress induction...

..Therefore, this differentiation pathway involves the modulation of protein phosphatases and this inhibition promotes the t-DCTN action on apoptosis induction...

..One of the two fused rings has a distorted-chair conformation and the other has a chair conformation. The molecules in the crystal are stabilized via O--H...O and C--H...O hydrogen bonds...

..Thus, DCR and DHC inhibit HL60 cell growth in vitro partly by inducing apoptosis and cell differentiation, but does not cause serious damage to immune cells according to our experimental conditions...

..In light of results obtained with DHC and natural trans-crotonin in the present study, we concluded that the A-ring of both diterpenes is not directly involved in the antiulcerogenic activity...

..The biological experiments, using the plant extracts and the terpenoids DCTN, CTN and AAA, are herein discussed...

..Thus, genus Ajuga has significant medicinal and economic importance...

..sylvestris, a medicinal plant species found in Cerrado and Atlantic Forest, led to the isolation of clerodane diterpenes 12-13 which showed effect on DNA...

..In this study the main neo-clerodane diterpenes (polystachynes A, B and D, as well as linearolactone) were isolated from the aerial parts of chia, and ..

..The acetyl derivative (10) of 1 and the methyl derivative (3) of 2 were found to be less active than the parent compounds. A complex of allantoin was also obtained from the berries, which on hydrolysis furnished pure allantoin (11)...

..and Avena sativa L. in Petri dish experiments. Parallel results have been obtained in experiments carried out to evaluate the subsequent growth of the seedlings of the target species in the presence of the tested compounds...

..Furthermore, the presence of a 4,18-epoxy/diol moiety was an important feature for both the antifeedant and the toxic/postingestive effects...

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Four new clerodane diterpenes, casearupestrins A-D (1-4), were isolated from the leaves of Casearia rupestris. Compounds 1 and 4 were acetylated to yield 2,7-di-O-acetylcasearupestrin A (5) and 2,6-di-O-acetylcasearupestrin D (6)...

Ten new neo-clerodane diterpenes, ajugaciliatins A-J (1-5, 8-12), along with 17 known analogues (6, 7, 13-27) were isolated from the whole plants of Ajuga ciliata Bunge...

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Nine clerodane diterpenes, solidagoic acids C-I (1-7), cleroda-3,13(14)-dien-16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were isolated and characterised from the ethanol-ethyl acetate (1:1) extract of ..

neo-Clerodane diterpenes of plant origin are molecules difficult to monitor due to their nonspecific UV/vis absorption...

..This review covers the isolation and structures of diterpenoids including labdanes, clerodanes, pimaranes, abietanes, kauranes, cembranes, taxanes and marine diterpenoids; 173 references are cited...

Two highly oxygenated clerodane diterpenes casearins U (1) and V (2) and two ent-kaurane diterpene glucosides sylvestrisides A (3) and B (4) were isolated from the leaves of Casearia sylvestris, together with 13 known compounds...

..Two new diterpenes (1 and 2) were obtained from the leaves of Tinospora rumphii, along with the known compounds tinotufolin D and vitexilactone. The structures of compounds 1 and 2 were established on the basis of spectroscopic studies...

..has revealed additional examples, palmadorins A-C (1-3), as the first three members of a new series of clerodane diterpenes. In this paper we describe their isolation, structure elucidation, and stereochemical analysis using a ..

Two new clerodane diterpenes were isolated from roots of Carex distachya Desf., a perennial plant widely distributed in the coastal area of the Mediterranean basin...

..These findings suggest that SalvA regulates the stimulant effects of cocaine through interactions with D1 receptor-mediated signaling in the dorsal striatum...

..The structure of the new compound was elucidated comprehensively using 1D and 2D NMR methods. Compounds showed effective antifeedancy against Plutella xylostella at 10 microg cm(-2) of leaf area...

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..5-6.6 μm...

..This prompted us to determine its target and, using molecular modelling, identify the interactions responsible for its specific antileishmanial activity...

Mass spectrometric fragmentation data of neo-clerodane diterpenes are almost inexistent but they can prove helpful for the qualitative and quantitative analysis of these compounds as well as for the identification of unknown compounds ..

..Compounds 3 and 4 existed as an equilibrium mixture. A mixture of compounds 3 and 4 was found to exhibit neurite outgrowth-promoting activities on NGF-mediated PC12 cells at concentrations ranging from 0.1 to 10.0 microM...

..The structures of the new compounds were elucidated by spectroscopic data analysis. Compounds 1-9 and 11 were evaluated on larvicidal activity against the fourth-instar larvae of Aedes albopictus and Culex pipens quinquefasciatus...

..2-8.3 microM...

..Compound 2 exhibited weak cytotoxic activity against HL-60 cells, with an IC(50) value of 41.4microM...

..c.) caused approximately 70% reduction in the peak effect of herkinorin (0.32 mg/kg) in females, indicating that this effect of herkinorin is prominently mediated outside the blood-brain barrier...

..The results support a biogenetic proposal to diterpenes found in the studied botanical species...

..Our results suggest that protecting salvinorin A derivatives from metabolism will prolong duration of action, but only when administered by routes giving slow absorption...

..Salvinorin A is rapidly eliminated after i.p. dosing, in accordance with its fast onset and short duration of action. Further, it appears to be a substrate for various oxidative enzymes and multi-drug resistant protein, P-gp...

..Recently, the neoclerodane diterpene, salvinorin A (12) has been investigated due to its unique pharmacological profile. This review will discuss the chemical methods used to chemically modify and synthesize 12...

..In the present study we investigated the possible anxiolytic- and antidepressant-like effects of the kappa-opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice...

..pendula was fractionated to get a hexane-soluble residue, which led to the isolation of four clerodane diterpenes: (-)-3α,16α-dihydroxycleroda-4(18),13(14)Z-dien-15,16-olide (1), (-)-3β,16α-dihydroxycleroda-4(18), 13(..

..Our findings confirm that ECD exhibits preventive effect against chemically induced HCC in rats. ECD can be a potent chemopreventive drug for HCC...

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..8-6.4 microM...

..As a result of this study, argutins A-H, eight new highly oxygenated clerodane diterpenes, were isolated from the plant Casearia arguta collected in Guatemala...

..We furthermore discuss structural changes in salvinorin A that may facilitate future use of its derivatives in human disease...

..Salvinorin A (SA) is a potent and highly selective kappa-opioid receptor (KOR) agonist with rapid kinetics and commensurate behavioral effects; however, brain regions associated with these effects have not been determined...

..These compounds were determined to be monoacetylated clerodane-type diterpenes based on spectroscopic evidence...

..The last two compounds were not reported earlier from this plant. The antibacterial activity of the diterpenoids were studied...

..The acid fraction of extracts from the aerial part of Croton schiedeanus afforded six cis-clerodane type diterpenoids. Two of them (1 and 4) are new natural compounds. Structural elucidation was achieved on the basis of their spectral data...

..of reversed-phase HPLC for the rapid isolation, identification and semi-preparative fractionation of neo-clerodane diterpenes from Ajuga remota, an extract from aerial parts of the plant was examined using a C18 column with UV ..

..Despite the beneficial antiulcerogenic activity of DHC, our results suggest that the long-term use of this compound may induce liver damage...

In our continuing search to discover bioactive compounds from natural products, we isolated six new clerodane diterpenes, caseamembrins A to F, from Casearia membranacea and examined their antiproliferative activities in human hormone-..

..In summary, only the natural compound exhibits anti-tumour efficacy and immunomodulatory actions in vivo, which may be related to its chemical structure...

..Semi-prep-HPLC proved to be a convenient purification procedure, occasionally being followed by TLC. The new compounds were assayed against Spodoptera littoralis and two of them were shown to have potent antifeedant activity...

..Salvinorin A thus represents the first known naturally occurring non-nitrogenous full agonist at kappa-opioid receptors...

..20%. This is the first analytical method developed for qualitative and quantitative analysis of nine neo-clerodane diterpenoids by HPLC with PDA detection...

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..Compositae), together with known ent-clerodane diterpenes (2, 3), eight known flavonoids (4-11) and 3, 5-dicaffeoylquinic acid (12)...

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..Cascarillin was shown to be a mixture of interconverting gamma-lactols and not a gamma-hydroxyaldehyde as previously reported...

..Three clerodanes were not previously described and their NMR spectroscopical data and MS fragmentation patterns are reported...

..Based on these observations, it can be suggested that gavage is the most effective method of administering t-DCTN. In addition, t-DCTN showed no cytotoxic effects in the bone marrow cells regardless of the route of exposure...

..Results of this work will direct further analog development of Salvinorin A (a next generation) and further define and refine our proposed computer binding and field models. ..

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..The goal of the proposed studies is to determine if salvinorin A modulates brain reward systems by altering dopamine-mediated signaling in the nucleus accumbens, a brain region involved in the regulation of reward. ..

..4) To demonstrate the novel compounds attenuate cocaine-induced behaviors. ..

..This work may lead to new pharmacotherapies that can alleviate aversive and dysphoric states associated with opiate withdrawal and perhaps reduce relapse to drug taking. ..

..4) To demonstrate the novel compounds attenuate cocaine-induced behaviors. ..

..Thus, these studies are likely to be more relevant to the potential human condition of MDMA-induced lasting neurochemical alterations and behavioral changes ..

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..In addition to the main projects, the Center will organize a competitive Pilot Project/Developmental program for the evaluation of new ideas and methods pertinent to the overall development of the Center. ..

..Behavior under these assays is sensitive to other abused drugs. Therefore, these assays may be of value in characterizing the effects of GHB. ..

..It is anticipated that a commercial nanospray interface for use in nanoLC-MS analysis will be available by the fall of 2003. ..

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..The availability of clones for these receptors would facilitate new drug design and provide new markers for disease linkage studies in families...

..Overall, the FT-MS instrument will sustain the high quality of biomedical research that is a hallmark of UAB. ..