clerodane diterpenes


Summary: A group of DITERPENES cyclized into 2-rings with a side-chain.

Top Publications

  1. Harding W, Schmidt M, Tidgewell K, Kannan P, Holden K, Gilmour B, et al. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A. J Nat Prod. 2006;69:107-12 pubmed
    ..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. ..
  2. Cifuente D, Borkowski E, Sosa M, Gianello J, Giordano O, Tonn C. Clerodane diterpenes from Baccharis sagittalis: insect antifeedant activity. Phytochemistry. 2002;61:899-905 pubmed
    ..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. ..
  3. Coll J. NMR shift data of neo-clerodane diterpenes from the genus Ajuga. Phytochem Anal. 2002;13:372-80 pubmed
  4. Coll J, Tandrón Y. Neo-clerodane diterpenes from Teucrium fruticans. Phytochemistry. 2004;65:387-92 pubmed
    ..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...
  5. Phan V, Chau V, Nguyen T, La V, Dan T, Nguyen H, et al. Aporphine alkaloids, clerodane diterpenes, and other constituents from Tinospora cordifolia. Fitoterapia. 2010;81:485-9 pubmed publisher
  6. Tang W, Hioki H, Harada K, Kubo M, Fukuyama Y. Clerodane diterpenoids with NGF-potentiating activity from Ptychopetalum olacoides. J Nat Prod. 2008;71:1760-3 pubmed publisher
    ..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...
  7. Ebner S, Roitman M, Potter D, Rachlin A, Chartoff E. Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology (Berl). 2010;210:241-52 pubmed publisher
    ..These data suggest that the effects of KOR activation on motivation are due, in part, to inhibition of phasic dopamine signaling in the NAc core. ..
  8. Puebla P, Correa S, Guerrero M, Carron R, San Feliciano A. New cis-clerodane diterpenoids from Croton schiedeanus. Chem Pharm Bull (Tokyo). 2005;53:328-9 pubmed
    ..Two of them (1 and 4) are new natural compounds. Structural elucidation was achieved on the basis of their spectral data. ..
  9. Wang Y, Chen Y, Xu W, Lee D, Ma Z, Rawls S, et al. 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. J Pharmacol Exp Ther. 2008;324:1073-83 pubmed
    ..Sal A at 10 mg/kg elicited neither antinociception nor hypothermia 30 min after administration to rats. In summary, MOM-Sal B is a potent and efficacious KOPR agonist with longer lasting in vivo effects than Sal A. ..

More Information

Publications108 found, 100 shown here

  1. Zhang J, Tang Y, Huang J, Li W, Zou Y, Tang G, et al. Bioactive diterpenoids from Croton laevigatus. Phytochemistry. 2017;144:151-158 pubmed publisher
    ..4 ± 0.8 and 6.0 ± 1.0 ?M, respectively, being more potent than the positive control, quercetin (IC50 = 13.1 ± 1.9 ?M). ..
  2. Rodriguez J, Haun M. Cytotoxicity of trans-dehydrocrotonin from Croton cajucara on V79 cells and rat hepatocytes. Planta Med. 1999;65:522-6 pubmed
    ..The bioactivation of DHC is mediated by cytochrome P450 and could generate metabolites that have no toxicity for V79 fibroblasts. ..
  3. Inan S, Lee D, Liu Chen L, Cowan A. Comparison of the diuretic effects of chemically diverse kappa opioid agonists in rats: nalfurafine, U50,488H, and salvinorin A. Naunyn Schmiedebergs Arch Pharmacol. 2009;379:263-70 pubmed publisher
    ..On the basis of our work, we (a) promote nalfurafine as a candidate diuretic to relieve water retention and (b) highlight salvinorin A as a kappa agonist that does not cause diuresis, probably because of its short duration of action. ..
  4. Aravind S, Balachandran J, Ramanujam Ganesh M, Krishna Kumari G. Further anti-feedant neo-clerodanes from Teucrium tomentosum. Nat Prod Res. 2010;24:7-12 pubmed publisher
    ..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. ..
  5. Juan Hikawczuk V, Lopez Verrilli M, Borkowski E, Sosa M, Giordano O, Saad J, et al. Antifeedant activity of neo-clerodane diterpenes from Baccharis flabellata Hook & Arn var. flabellata toward Tribolium castaneum Herbst: structure-activity relationships. Nat Prod Res. 2006;20:813-9 pubmed
    In order to establish structure-activity relationships, nine neo-clerodane diterpenes isolated from the acetone extract of aerial parts of Baccharis flabellata Hook & Arn var...
  6. Braida D, Limonta V, Pegorini S, Zani A, Guerini Rocco C, Gori E, et al. Hallucinatory and rewarding effect of salvinorin A in zebrafish: kappa-opioid and CB1-cannabinoid receptor involvement. Psychopharmacology (Berl). 2007;190:441-8 pubmed
    ..These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors. ..
  7. Xu H, Wang X, Partilla J, Bishop Mathis K, Benaderet T, Dersch C, et al. Differential effects of opioid agonists on G protein expression in CHO cells expressing cloned human opioid receptors. Brain Res Bull. 2008;77:49-54 pubmed publisher
  8. Li X, Yang L, Zhao Y, Wang R, Xu G, Zheng Y, et al. Tetranorclerodanes and clerodane-type diterpene glycosides from Dicranopteris dichotoma. J Nat Prod. 2007;70:265-8 pubmed
    ..The structures of these new compounds were established by a combination of 1D and 2D NMR techniques, MS, and acid hydrolysis. Compound 8 showed modest anti-HIV-1 activity. ..
  9. Ahmad V, Khan A, Farooq U, Kousar F, Khan S, Hussain J. Two new trans-clerodane diterpenoids from Otostegia limbata. J Asian Nat Prod Res. 2007;9:91-5 pubmed
    ..Their structures and the relative configuration were established on the basis of spectral methods, especially two-dimensional (2D) NMR techniques. ..
  10. Calzada F, Yepez Mulia L, Tapia Contreras A, Bautista E, Maldonado E, Ortega A. Evaluation of the antiprotozoal activity of neo-clerodane type diterpenes from Salvia polystachya against Entamoeba histolytica and Giardia lamblia. Phytother Res. 2010;24:662-5 pubmed publisher
    ..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 ..
  11. Roengsumran S, Musikul K, Petsom A, Vilaivan T, Sangvanich P, Pornpakakul S, et al. Croblongifolin, a new anticancer clerodane from Croton oblongifolius. Planta Med. 2002;68:274-7 pubmed
    ..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. ..
  12. Das B, Ramu R, Venkateswarlu K, Rao Y, Reddy M, Ramakrishna K, et al. New clerodane diterpenoids from the aerial parts of Pulicaria wightiana. Chem Biodivers. 2006;3:175-9 pubmed
    ..Their structures were established based on spectroscopic data, and their antibacterial activities were evaluated (Table 2). ..
  13. Anazetti M, Melo P, Duran N, Haun M. Comparative cytotoxicity of dimethylamide-crotonin in the promyelocytic leukemia cell line (HL60) and human peripheral blood mononuclear cells. Toxicology. 2003;188:261-74 pubmed
    ..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. ..
  14. Giner J, Kiemle D, Kutrzeba L, Zjawiony J. Unambiguous NMR spectral assignments of salvinorin A. Magn Reson Chem. 2007;45:351-4 pubmed
    ..Virtual coupling was observed for the protons at C-2, C-3 and C-4 in the 600 MHz (1)H spectrum in CDCl(3). The complete assignments of the (1)H and (13)C NMR spectra of salvinorin B are also reported. ..
  15. Butelman E, Prisinzano T, Deng H, Rus S, Kreek M. Unconditioned behavioral effects of the powerful kappa-opioid hallucinogen salvinorin A in nonhuman primates: fast onset and entry into cerebrospinal fluid. J Pharmacol Exp Ther. 2009;328:588-97 pubmed publisher
    ..These are the first studies documenting rapid unconditioned effects of salvinorin A in a primate species, consistent with descriptive reports of rapid and robust effects of this powerful hallucinogen in humans. ..
  16. Kennedy J, Wiseman J. Direct analysis of Salvia divinorum leaves for salvinorin A by thin layer chromatography and desorption electrospray ionization multi-stage tandem mass spectrometry. Rapid Commun Mass Spectrom. 2010;24:1305-11 pubmed publisher
    ..The present study provides an example of both the direct analysis of intact plant materials for screening illicit substances and the coupling of TLC and DESI-MS as a simple method for the examination of natural products. ..
  17. Roth B, Baner K, Westkaemper R, Siebert D, Rice K, Steinberg S, et al. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci U S A. 2002;99:11934-9 pubmed
    ..g., schizophrenia, dementia, and bipolar disorders). Additionally, these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception. ..
  18. Barnes S, Prasain J, Wang C, Moore D. Applications of LC-MS in the study of the uptake, distribution, metabolism and excretion of bioactive polyphenols from dietary supplements. Life Sci. 2006;78:2054-9 pubmed
    ..In this paper, applications of these methods are described for the analysis of isoflavones, salvinorin A, synephrine isomers and their metabolites in serum, urine and aqueous humor. ..
  19. Dai S, Shen L, Ren Y. Two new neo-clerodane diterpenoids from Scutellaria barbata. J Integr Plant Biol. 2008;50:699-702 pubmed publisher
    ..5-6.7 microM. ..
  20. Simpson D, Lovell K, Lozama A, Han N, Day V, Dersch C, et al. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors. Org Biomol Chem. 2009;7:3748-56 pubmed publisher
    ..This indicates that additional structural modifications of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity. ..
  21. Melo P, Duran N, Haun M. Derivatives of dehydrocrotonin, a diterpene lactone isolated from Croton cajucara: cytotoxicity in rat cultured hepatocytes and in V79 cells. Hum Exp Toxicol. 2002;21:281-8 pubmed
    ..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. ..
  22. Qin H, Li Z. Clerodane-type diterpenoids from Nannoglottis ravida. Phytochemistry. 2004;65:2533-7 pubmed
    ..Their structures and stereochemistry were established by spectroscopic methods, including X-ray crystallographic diffraction analysis of ravidin A. Their significance in terms of the chemotaxonomy of Nannoglottis is discussed. ..
  23. Silva R, Oliveira F, Cunha K, Maia J, Maciel M, Pinto A, et al. Cardiovascular effects of trans-dehydrocrotonin, a diterpene from Croton cajucara in rats. Vascul Pharmacol. 2005;43:11-8 pubmed
    ..These data indicate the hypotensive and bradycardia effects of t-DCTN, possibly related in part to the release of nitric oxide and in part to direct effects on vascular smooth muscle, and cardiac pacemaker activity. ..
  24. Niu H, Zeng D, Long C, Peng Y, Wang Y, Luo J, et al. Clerodane diterpenoids and prenylated flavonoids from Dodonaea viscosa. J Asian Nat Prod Res. 2010;12:7-14 pubmed publisher
    ..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. ..
  25. Farooq U, Khan A, Ahmad V, Khan S, Farooq R, Pervez A, et al. Complete (1)H and (13)C NMR assignments of two new trans-clerodane diterpenoids from Otostegia limbata. Magn Reson Chem. 2007;45:766-9 pubmed
    ..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. ..
  26. Echiburu Chau C, Pastén L, Parra C, Borquez J, Mocan A, Simirgiotis M. High resolution UHPLC-MS characterization and isolation of main compounds from the antioxidant medicinal plant Parastrephia lucida (Meyen). Saudi Pharm J. 2017;25:1032-1039 pubmed publisher
    ..Forty-two metabolites including several phenolic acids, flavonoids, coumarines, tremetones and ent-clerodane diterpenes were accurately identified for the first time in the resin of the medicinal plant Parastrephia lucida..
  27. Salah M, Bedir E, Toyang N, Khan I, Harries M, Wedge D. Antifungal clerodane diterpenes from Macaranga monandra (L) Muell. et Arg. (Euphorbiaceae). J Agric Food Chem. 2003;51:7607-10 pubmed
    ..A 96-well microbioassay revealed that kolavenic acid and 2-oxo-kolavenic acid produced moderate growth inhibition in Phomopsis viticola and Botrytis cinerea. ..
  28. Rotella D. American Chemical Society--233rd National Meeting. CNS, cancer and cardiovascular targets. 25-29 March 2007, Chicago, IL, USA. IDrugs. 2007;10:310-2 pubmed
  29. Castro A, Moco S, Coll J, Vervoort J. LC-MS-SPE-NMR for the isolation and characterization of neo-clerodane diterpenoids from Teucrium luteum subsp. flavovirens (perpendicular). J Nat Prod. 2010;73:962-5 pubmed publisher
    neo-Clerodane diterpenes of plant origin are molecules difficult to monitor due to their nonspecific UV/vis absorption...
  30. Rodgen S, Schaus S. Efficient construction of the clerodane decalin core by an asymmetric Morita-Baylis-Hillman reaction/Lewis acid promoted annulation strategy. Angew Chem Int Ed Engl. 2006;45:4929-32 pubmed
  31. Brito A, Rodriguez J, Hiruma Lima C, Haun M, Nunes D. Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara. Planta Med. 1998;64:126-9 pubmed
    ..The high yields of DHC obtained from dried C. cajucara barks as well as its good antiulcerogenic activity and low toxicity support the pharmacological study of this compound as a potential new antiulcerogenic drug. ..
  32. Guerrero M, Puebla P, Carron R, Martin M, San Roman L. Vasorelaxant effect of new neo-clerodane diterpenoids isolated from Croton schiedeanus. J Ethnopharmacol. 2004;94:185-9 pubmed
    ..These results suggest that Croton schiedeanus induces its effects via the synergistic actions of several vasodilator substances, among which neo-clerodane diterpenoids play an important role...
  33. McCurdy C, Sufka K, Smith G, Warnick J, Nieto M. Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist. Pharmacol Biochem Behav. 2006;83:109-13 pubmed
    ..These findings demonstrate that salvinorin A produces a KOP mediated antinociceptive effect with a short duration of action. ..
  34. Freire A, de Assis C, Frick A, da Silva Melo P, Haun M, Aoyama H, et al. Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin. Leuk Res. 2003;27:823-9 pubmed
    ..Therefore, this differentiation pathway involves the modulation of protein phosphatases and this inhibition promotes the t-DCTN action on apoptosis induction. ..
  35. Jullian V, Bonduelle C, Valentin A, Acebey L, Duigou A, Prévost M, et al. New clerodane diterpenoids from Laetia procera (Poepp.) Eichler (Flacourtiaceae), with antiplasmodial and antileishmanial activities. Bioorg Med Chem Lett. 2005;15:5065-70 pubmed
    ..The most active compound showed a selectivity index of 6.8. Some of these compounds also displayed activities against Leishmania amazonensis amastigote axenic stages and promastigote. ..
  36. Beerepoot P, Lam V, Luu A, Tsoi B, Siebert D, Szechtman H. Effects of salvinorin A on locomotor sensitization to D2/D3 dopamine agonist quinpirole. Neurosci Lett. 2008;446:101-4 pubmed publisher
    ..Moreover, the opposite effects of high and low salvinorin A doses suggest that salvinorin A can produce bidirectional modulation of sensitization to dopamine agonists. ..
  37. Butelman E, Rus S, Prisinzano T, Kreek M. The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects. Psychopharmacology (Berl). 2010;210:253-62 pubmed publisher
  38. Maurya R, Manhas L, Gupta P, Mishra P, Singh G, Yadav P. Amritosides A, B, C and D: clerodane furano diterpene glucosides from Tinospora cordifolia. Phytochemistry. 2004;65:2051-5 pubmed
    ..Four new clerodane furano diterpene glucosides (amritosides A, B, C and D) were isolated as their acetates from Tinospora cordifolia stems. The structures of these compounds were established on the basis of spectroscopic studies...
  39. Ahmad V, Khan A, Farooq U, Kousar F, Khan S, Nawaz S, et al. Three new cholinesterase-inhibiting cis-clerodane diterpenoids from Otostegia limbata. Chem Pharm Bull (Tokyo). 2005;53:378-81 pubmed
    ..Compounds 1-3 displayed inhibitory potential in a concentration-dependent manner against acetylcholinesterase (AChE; EC and butyrylcholinesterase (BChE; EC enzymes, respectively. ..
  40. Lee H, Kim Y, Choi I, Min B, Shim S. Two novel neo-clerodane diterpenoids from Scutellaria barbata. Bioorg Med Chem Lett. 2010;20:288-90 pubmed publisher
    ..Compound 2 exhibited weak cytotoxic activity against HL-60 cells, with an IC(50) value of 41.4microM. ..
  41. Katayama K, Shimazaki K, Tazaki H, Hasa Y, Miyoshi M, Koshino H, et al. Parvitexins A-E, clerodane-type diterpenes isolated from the in vitro-cultured liverwort, Scapania parvitexta. Biosci Biotechnol Biochem. 2007;71:2751-8 pubmed
    ..These compounds were determined to be monoacetylated clerodane-type diterpenes based on spectroscopic evidence. ..
  42. Rodriguez J, Hiruma Lima C, Souza Brito A. Antiulcer activity and subacute toxicity of trans-dehydrocrotonin from Croton cajucara. Hum Exp Toxicol. 2004;23:455-61 pubmed
    ..Despite the beneficial antiulcerogenic activity of DHC, our results suggest that the long-term use of this compound may induce liver damage. ..
  43. Vortherms T, Mosier P, Westkaemper R, Roth B. Differential helical orientations among related G protein-coupled receptors provide a novel mechanism for selectivity. Studies with salvinorin A and the kappa-opioid receptor. J Biol Chem. 2007;282:3146-56 pubmed
    ..These findings imply that differences in the helical orientation of helix 2 are critical for the selectivity of salvinorin A binding to KOR and provide a structurally novel basis for ligand selectivity. ..
  44. Dai S, Liang D, Ren Y, Liu K, Shen L. New neo-clerodane diterpenoid alkaloids from Scutellaria barbata with cytotoxic activities. Chem Pharm Bull (Tokyo). 2008;56:207-9 pubmed
    ..2-8.3 microM. ..
  45. Jermain J, Evans H. Analyzing salvia divinorum and its active ingredient salvinorin a utilizing thin layer chromatography and gas chromatography/mass spectrometry. J Forensic Sci. 2009;54:612-6 pubmed publisher
    ..By utilizing these techniques, criminalists are now able to confirm the presence of salvinorin A in a submitted plant material suspected to be Salvia divinorum. ..
  46. Silva R, Santos F, Rao V, Maciel M, Pinto A. The lipid-lowering effect of trans-dehydrocrotonin, a clerodane diterpene from Croton cajucara Benth. in mice fed on high-fat diet. J Pharm Pharmacol. 2001;53:535-9 pubmed
    ..These results indicate that orally administered trans-dehydrocrotonin is effective in suppressing high-fat-diet-induced hyperlipidaemia in mice and suggest its likely beneficial use as anti-atherogenic agent. ..
  47. Harinantenaina L, Takahara Y, Nishizawa T, Kohchi C, Soma G, Asakawa Y. Chemical constituents of malagasy liverworts, part V: prenyl bibenzyls and clerodane diterpenoids with nitric oxide inhibitory activity from Radula appressa and Thysananthus spathulistipus. Chem Pharm Bull (Tokyo). 2006;54:1046-9 pubmed
    ..All of the isolated compounds inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the greatest inhibition was attributed to compound 5, with an IC50 value of 4.5 microM. ..
  48. Groer C, Tidgewell K, Moyer R, Harding W, Rothman R, Prisinzano T, et al. An opioid agonist that does not induce mu-opioid receptor--arrestin interactions or receptor internalization. Mol Pharmacol. 2007;71:549-57 pubmed
  49. Braida D, Limonta V, Capurro V, Fadda P, Rubino T, Mascia P, et al. Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Biol Psychiatry. 2008;63:286-92 pubmed
    ..These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats. ..
  50. Li W, Wei K, Fu H, Koike K. Structure and absolute configuration of clerodane diterpene glycosides and a rearranged cadinane sesquiterpene glycoside from the stems of Tinospora sinensis. J Nat Prod. 2007;70:1971-6 pubmed
    ..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. ..
  51. Kane B, McCurdy C, Ferguson D. Toward a structure-based model of salvinorin A recognition of the kappa-opioid receptor. J Med Chem. 2008;51:1824-30 pubmed publisher
    ..The model explains the role that hydrophobic contacts play in binding this lipophilic ligand and gives insight into the structural basis to the mu-opioid receptor selectivity of 2'-benzoyl salvinorin (herkinorin). ..
  52. Hooker J, Xu Y, Schiffer W, Shea C, Carter P, Fowler J. Pharmacokinetics of the potent hallucinogen, salvinorin A in primates parallels the rapid onset and short duration of effects in humans. Neuroimage. 2008;41:1044-50 pubmed publisher
    ..divinorum when smoked. The effects of salvinorin A may occur at <10 mug in the human brain, emphasizing its remarkable potency. ..
  53. Seeman P, Guan H, Hirbec H. Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse. 2009;63:698-704 pubmed publisher
    ..It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions. ..
  54. Teksin Z, Lee I, Nemieboka N, Othman A, Upreti V, Hassan H, et al. Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen. Eur J Pharm Biopharm. 2009;72:471-7 pubmed publisher
    ..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. ..
  55. Kutrzeba L, Li X, Ding Y, Ferreira D, Zjawiony J. Intramolecular transacetylation in salvinorins D and E. J Nat Prod. 2010;73:707-8 pubmed publisher
    ..The presence of both compounds was readily observed in the (1)H NMR spectrum. This spontaneous formation of the mixture of isomers occurs via a dynamic intramolecular transacetylation process. ..
  56. Grynberg N, Echevarria A, Lima J, Pamplona S, Pinto A, Maciel M. Anti-tumour activity of two 19-nor-clerodane diterpenes, trans-dehydrocrotonin and trans-crotonin, from Croton cajucara. Planta Med. 1999;65:687-9 pubmed
    ..A significant TNF alpha activity was detected in Ehrlich tumour-bearing mice treated with DCTN suggesting an enhanced immune function. ..
  57. Mambu L, Ramanandraibe V, Martin M, Blond A, Grellier P, Frappier F. Constituents of Burasaïa madagascarensis: a new clerodane-type diterpene. Planta Med. 2002;68:377-9 pubmed
    ..The structures were established by the interpretation of the spectral data. All the described compounds exhibited weak antimalarial activity. ..
  58. Vaccarini C, Palacios S, Meragelman K, Sosa V. Antifeedant activity of metabolites from Viguiera tucumanensis. Nat Prod Lett. 2002;16:323-7 pubmed
    ..tucumanensis, were isolated and bioassayed. The clerodane 1 showed higher antifeedant activity than other related compounds. Structure-activity relationships are also discussed. ..
  59. Urzua A, Torres R, Mendoza L, Delle Monache F. Antibacterial new clerodane diterpenes from the surface of Haplopappus foliosus. Planta Med. 2003;69:675-7 pubmed reported. Purification of the two active fractions yielded 2-alpha-hydroxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (1) and 2-alpha-acetoxy- cis-cleroda-3,13(Z),8(17)-trien-15-oic acid (2), two new clerodane diterpenes.
  60. Arns S, Barriault L. Concise synthesis of the neo-clerodane skeleton of teucrolivin A using a pericyclic reaction cascade. J Org Chem. 2006;71:1809-16 pubmed
  61. Hussain J, Jamila N, Khan F, Devkota K, Shah M, Anwar S. Nepetanal and nepetanoate: a new diterpene aldehyde and a benzene derivative ester from Nepeta juncea. Magn Reson Chem. 2009;47:625-7 pubmed publisher
    ..The structures of the isolated compounds were elucidated by means of modern spectroscopic techniques and comparison with literature data...
  62. Kutrzeba L, Ferreira D, Zjawiony J. Salvinorins J from Salvia divinorum: mutarotation in the neoclerodane system. J Nat Prod. 2009;72:1361-3 pubmed publisher
    ..Salvinorins J (2) represent an example of a neoclerodane hemiacetal (lactol) susceptible to mutarotation with the formation of an equilibrium mixture of C-17 epimers. ..
  63. Yan F, Bikbulatov R, Mocanu V, Dicheva N, Parker C, Wetsel W, et al. Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor. Biochemistry. 2009;48:6898-908 pubmed publisher
    ..These studies provide direct evidence of the presence of a free cysteine in the agonist-bound state of the KOR and provide novel insights into the mechanism by which salvinorin A binds to and activates the KOR. ..
  64. Dai S, Peng W, Zhang D, Shen L, Wang W, Ren Y. Cytotoxic neo-clerodane diterpenoid alkaloids from Scutellaria barbata. J Nat Prod. 2009;72:1793-7 pubmed publisher
    ..8-6.4 microM. ..
  65. Tejeda H, Chefer V, Zapata A, Shippenberg T. The effects of kappa-opioid receptor ligands on prepulse inhibition and CRF-induced prepulse inhibition deficits in the rat. Psychopharmacology (Berl). 2010;210:231-40 pubmed publisher
    ..Additional studies, however, examining whether dysregulation of this opioid system contributes to cognitive deficits and other behavioral abnormalities associated with psychiatric disorders are warranted. ..
  66. Kihampa C, Nkunya M, Joseph C, Magesa S, Hassanali A, Heydenreiche M, et al. Antimosquito and antimicrobial clerodanoids and a chlorobenzenoid from Tessmannia species. Nat Prod Commun. 2010;5:175-8 pubmed
    ..martiniana var matiniana. Structures were established based on interpretation of spectroscopic data. Some of the compounds exhibited significant antimosquito, antifungal and antibacterial activities. ..
  67. Walentiny D, Vann R, Warner J, King L, Seltzman H, Navarro H, et al. Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents. Psychopharmacology (Berl). 2010;210:275-84 pubmed publisher
    ..Further, the results suggest that rimonabant reversal of salvinorin A effects in previous studies may be explained in part by rimonabant attenuation of KOR activation. ..
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    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 ..
  69. Jung H, Chung S, Nam J, Chae S, Lee Y, Seo E, et al. Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana. Chem Biodivers. 2010;7:2095-101 pubmed publisher
    ..These results suggest that compound 1 inhibits the functioning of P-gp and, therefore, can be developed as an MDR-reversing agent. ..
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    ..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. ..
  71. Hayashi K, Nakanishi Y, Bastow K, Cragg G, Nozaki H, Lee K. Antitumor agents. Part 212. Bucidarasins A-C, three new cytotoxic clerodane diterpenes from Bucida buceras. Bioorg Med Chem Lett. 2002;12:345-8 pubmed
    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...
  72. Huang D, Shen Y, Wu C, Huang Y, Kung F, Teng C, et al. Investigation of extrinsic and intrinsic apoptosis pathways of new clerodane diterpenoids in human prostate cancer PC-3 cells. Eur J Pharmacol. 2004;503:17-24 pubmed
    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-..
  73. Bianco A, Ramunno A, Serrilli A, Lo Castro M, Ballero M, Serafini M. Phytochemical characters of Teucrium marum from Sardinia: an endemic plant. Nat Prod Res. 2004;18:557-64 pubmed
    ..A new clerodane, teumarin B, was isolated and identified by 1H- and 13C-NMR spectra analysis. The endemic character of this plant was further confirmed. Teumarin B showed cytotoxic properties. ..
  74. Fontana G, Savona G, Rodriguez B. Complete 1H and 13C NMR assignments of clerodane diterpenoids of Salvia splendens. Magn Reson Chem. 2006;44:962-5 pubmed
    Unambiguous and complete assignments of 1H and 13C NMR chemical shifts for five clerodane diterpenes, four of them isolated from Salvia splendens (salviarin, splendidin and splenolides A and B) and one obtained by acetylation of ..
  75. Shirota O, Nagamatsu K, Sekita S. Neo-clerodane diterpenes from the hallucinogenic sage Salvia divinorum. J Nat Prod. 2006;69:1782-6 pubmed
    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, ..
  76. Poersch A, dos Santos F, Maciel M, de Câmara J, de Castro Dantas T, de Syllos Cólus I. Protective effect of DCTN (trans-dehydrocrotonin) against induction of micronuclei and apoptosis by different mutagenic agents in vitro. Mutat Res. 2007;629:14-23 pubmed
    ..These results together with findings reported for DCTN in vivo, support the indication of this active principle at these concentrations for therapeutic use. ..
  77. Williams R, Norris A, Miller J, Birkinshaw C, Ratovoson F, Andriantsiferana R, et al. Cytotoxic clerodane diterpenoids and their hydrolysis products from Casearia nigrescens from the rainforest of Madagascar. J Nat Prod. 2007;70:206-9 pubmed
    ..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...
  78. Simpson D, Katavic P, Lozama A, Harding W, Parrish D, Deschamps J, et al. Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues. J Med Chem. 2007;50:3596-603 pubmed
    ..This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications. ..
  79. Tsujikawa K, Kuwayama K, Miyaguchi H, Kanamori T, Iwata Y, Yoshida T, et al. Determination of salvinorin A and salvinorin B in Salvia divinorum-related products circulated in Japan. Forensic Sci Int. 2008;180:105-9 pubmed publisher
    ..2-5.0/0.10-0.17 in the dried leaf products and 4.1-38.9/0.26-2.42 in the "concentrated extract" products. These findings would be useful for analysis of S. divinorum-related products circulated in the drug market. ..
  80. Baker L, Panos J, Killinger B, Peet M, BELL L, Haliw L, et al. Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats. Psychopharmacology (Berl). 2009;203:203-11 pubmed publisher
    ..Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy. ..
  81. Wang W, Ali Z, Li X, Smillie T, Guo D, Khan I. New clerodane diterpenoids from Casearia sylvestris. Fitoterapia. 2009;80:404-7 pubmed publisher
    ..Their structures were determined by extensive NMR techniques...
  82. Dai S, Peng W, Shen L, Zhang D, Ren Y. Two new neo-clerodane diterpenoid alkaloids from Scutellaria barbata with cytotoxic activities. J Asian Nat Prod Res. 2009;11:451-6 pubmed publisher
    ..1-5.7 microM. ..
  83. Liu C, Zhu R, Liu R, Li H, Shan L, Xu X, et al. cis-Clerodane diterpenoids from the liverwort Gottschelia schizopleura and their cytotoxic activity. Planta Med. 2009;75:1597-601 pubmed publisher
    ..Compound 1 showed moderate inhibition against MDA-MB-435 and LOVO cells. ..
  84. Vieira G, Gonçalves T, Regasini L, Ferreira P, Pessoa C, Costa Lotufo L, et al. Cytotoxic clerodane diterpenoids from Casearia obliqua. J Nat Prod. 2009;72:1847-50 pubmed publisher
    A crude bioactive EtOH extract of the twigs of Casearia obliqua afforded two new clerodane diterpenes, caseobliquins A (1) and B (2)...
  85. dos Santos A, Ferreira P, Vieira Júnior G, Perez C, Gomes Tininis A, Silva G, et al. Casearin X, its degradation product and other clerodane diterpenes from leaves of Casearia sylvestris: evaluation of cytotoxicity against normal and tumor human cells. Chem Biodivers. 2010;7:205-15 pubmed publisher
    ..Casearin X dialdehyde was not cytotoxic to cancer cells indicating that the occurrence of these CO groups at C(18) and C(19) is incompatible with the cytotoxic activity...
  86. Coll J, Tandrón Y. Isolation and structure elucidation of three neo-clerodane diterpenes from Teucrium fruticans L. (LABIATAE). Phytochemistry. 2005;66:2298-303 pubmed
    ..Compounds 9-11 showed low antifeedant activity and the feeding ratio of 12 was moderate-low. None of the tested compounds displayed significant activity against R. solani. ..
  87. Medana C, Massolino C, Pazzi M, Baiocchi C. Determination of salvinorins and divinatorins in Salvia divinorum leaves by liquid chromatography/multistage mass spectrometry. Rapid Commun Mass Spectrom. 2006;20:131-6 pubmed
    ..The importance of LC in herbal extract determination and the chemical diagnostic power of MS(n) in the analysis of classes of natural organic products are discussed. ..
  88. Kutrzeba L, Dayan F, Howell J, Feng J, Giner J, Zjawiony J. Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway. Phytochemistry. 2007;68:1872-81 pubmed
  89. Li Y, Husbands S, Mahon M, Traynor J, Rowan M. Isolation and chemical modification of clerodane diterpenoids from Salvia species as potential agonists at the kappa-opioid receptor. Chem Biodivers. 2007;4:1586-93 pubmed
    ..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. ..
  90. Maruyama T, Kamakura H, Kikura Hanajiri R, Goda Y. [Authentication and ultra performance liquid chromatography (UPLC)/MS analysis of magic mint, Salvia divinorum and its related plants]. Yakugaku Zasshi. 2008;128:179-83 pubmed
    ..divinorum from the tested cultivars. In conclusion, the authentication method is considered to be useful for the practical regulation of S. divinorum due to its simplicity and accuracy. ..
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    ..Differences in the interaction of salvinorin and synthetic KOPr agonists with cocaine suggest that the pharmacology of these agents may differ. ..
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