Kavalactone pharmacophores for major cellular drug targets

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 1, 2011, Pages 79-83

  Rowe, A ^a   Narlawar, R ^a   Groundwater, P W ^a   Ramzan, I ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

Conformational isomerism; Kavalactone; Molecular targets; Pharmacophore

Indexed keywords

4 AMINOBUTYRIC ACID A RECEPTOR; 7,8 DIHYDROKAVAIN; AMINE OXIDASE (FLAVIN CONTAINING) ISOENZYME B; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; CYTOCHROME P450; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; DESMETHOXYYANGONIN; DIHYDROMETHYSTICIN; GLYCOPROTEIN P; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KAVA EXTRACT; KAVALACTONE; LACTONE DERIVATIVE; METHYSTICIN; PREGNANE X RECEPTOR; PROSTAGLANDIN SYNTHASE; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG; YANGONIN;

ARTICLE; BINDING COMPETITION; DRUG BINDING SITE; DRUG CONFORMATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG TARGETING; NONHUMAN; PHARMACOPHORE; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELLS; DRUG DISCOVERY; HUMANS; LACTONES; PYRONES;

EID: 78650916335     PISSN: 13895575     EISSN: None     Source Type: Journal    
DOI: 10.2174/138955711793564088     Document Type: Article

References (20)

1. Lindstrom, L. In Kava from Ethnology to Pharmacology. Singh, Y.N., Ed.; CRC Press: Boca Raton, 2004; Vol. 76, pp 10-28.
2. Bilia, A.R.; Gallon, S.; Vincieri, F.F. Kava-kava and anxiety: growing knowledge about the efficacy and safety. Life Sci., 2002, 70, 2581-2597.
3. Anke, J.; Ramzan, I. Pharmacokinetic and pharmacodynamic drug interactions with Kava (Piper methysticum Forst. f.). J. Ethnopharmacol., 2004, 93, 153-160.
4. Singh, Y.N.; Singh, N.N.; Bilia, A.R.; Gallon, S.; Vincieri, F.F. Therapeutic potential of kava in the treatment of anxiety disorders. CNS Drugs, 2002, 16, 731-743.
5. Zhou, S.; Lim, L.Y.; Chowbay, B. Herbal modulation of Pglycoprotein. Drug Metab. Rev., 2004, 36, 57-104.
6. Weiss, J.; Sauer, A.; Frank, A.; Unger, M. Extracts and kavalactones of Piper methysticum G. Forst (Kava-kava) inhibit pglycoprotein in vitro. Drug Metab. Dispos., 2005, 33, 1580-1583.
7. Pombo, S.; Levy, P.; Bicho, M.; Ismail, F.; Cardoso, J.M.N. Neuropsychological function and platelet monoamine oxidase activity levels in type I alcoholic patients. Alcohol Alcohol., 2008, 43, 423-430.
8. Uebelhack, R.; Franke, L.; Schewe, H.J. Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry, 1998, 31, 187-192.
9. Cryer, B.; Dubois, A. The advent of highly selective inhibitors of cyclooxygenase - a review. Prostaglandins Other Lipid Mediat., 1998, 56, 341-361.
10. Wu, D.; Yu, L.; Nair, M.G.; DeWitt, D.L.; Ramsewak, R.S. Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. Phytomedicine, 2002, 9, 41-47.
11. Folmer, F.; Blasius, R.; Morceau, F.; Tabudravu, J.; Dicato, M.; Jaspars, M.; Diederich, M. Inhibition of TNF-induced activation of nuclear factor B by kava (Piper methysticum) derivatives. Biochem. Pharmacol., 2006, 71, 1206-1218.
12. Shaik, A.A.; Hermanson, D.L.; Xing, C. Identification of methysticin as a potent and non-toxic NF-B inhibitor from kava, potentially responsible for kava's chemopreventive activity. Bioorg. Med. Chem. Lett., 2009, 19, 5732-5736.
13. Pollastri, M.P.; Whitty, A.; Merrill, J.C.; Tang, X.; Ashton, T.D.; Amar, S. Identification and characterization of kava-derived compounds mediating TNF suppression. Chem. Biol. Drug Des., 2009, 74, 121-128.
14. Shord, S.S.; Shah, K.; Lukose, A. Drug-botanical interactions: a review of the laboratory, animal and human data for 8 common botanicals. Integr. Cancer Ther., 2009, 8, 208-227.
15. Pelkonen, O.; Turpeinen, M.; Hakkola, J.; Honkakoski, P.; Hukkanen, J.; Raunio, H. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch. Toxicol., 2008, 82, 667-715.
16. Raucy, J.L. Regulation of CYP3A4 expression in human hepatocytes by pharmaceuticals and natural products. Drug Metab. Dispos., 2003, 31, 533-539.
17. Tompkins, L.M.; Wallace, A.D. Mechanisms of cytochrome P450 induction. J. Biochem. Mol. Toxicol., 2007, 21, 176-181.
18. Ma, Y.; Sachdeva, K.; Liu, J.; Ford, M.; Yang, D.; Khan, I.A.; Chichester, C.O.; Yan, B. Desmethoxyyangonin and dihydromethysticin are two major pharmacological kavalactones with marked activity on the induction of Cyp3A23. Drug Metab. Dispos., 2004, 32, 1317-1324.
19. Vijayan, R.S.K.; Ghoshal, N. Structural basis for ligand recognition at the benzodiazepine binding site of GABAa alpha-3 receptor, and pharmacophore-based virtual screening approach. J. Mol. Graph. Model., 2008, 27, 286-298.
20. Davies, L.P.; Drew, C.A.; Duffield, P.; Johnston, G.A.R.; Jamieson, D.D. Kava pyrones and resin: studies on GABAa, GABAb and benzodiazepine binding sites in rodent brain. Pharmacol. Toxicol., 1992, 71, 120-126.