Computer-aided discovery, validation, and mechanistic characterization of novel neolignan activators of peroxisome proliferator-activated receptor γ

Molecular Pharmacology

Volumn 77, Issue 4, 2010, Pages 559-566

  Fakhrudin, Nanang ^a,d   Ladurner, Angela ^a   Atanasov, Atanas Georgiev ^a   Heiss, Elke H ^a   Baumgartner, Lisa ^b   Markt, Patrick ^b,c   Schuster, Daniela ^b   Ellmerer, Ernst P ^b   Wolber, Gerhard ^b,c   Rollinger, Judith M ^b   Stuppner, Hermann ^b   Dirsch, Verena M ^a  

^a UNIVERSITY OF VIENNA   (Austria)

^b UNIVERSITY OF INNSBRUCK   (Austria)

^c Inte:Ligand GmbH   (Austria)

^d GADJAH MADA UNIVERSITY   (Indonesia)

Author keywords

[No Author keywords available]

Indexed keywords

DIEUGENOL; LUCIFERASE; MAGNOLOL; NEOLIGNAN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PIOGLITAZONE; TETRAHYDRODIEUGENOL; UNCLASSIFIED DRUG;

ARTICLE; CELL DIFFERENTIATION; COMPUTER ANALYSIS; CONTROLLED STUDY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; PRIORITY JOURNAL; PROADIPOCYTE; PROTEIN ANALYSIS; PROTEIN EXPRESSION; RECEPTOR BINDING;

3T3-L1 CELLS; ADIPOCYTES; ANIMALS; BINDING, COMPETITIVE; CELL DIFFERENTIATION; DRUG DISCOVERY; HUMANS; LUCIFERASES; MICE; PPAR GAMMA; SOFTWARE; TRANSCRIPTIONAL ACTIVATION;

EID: 77950253421     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.109.062141     Document Type: Article

References (36)

1. Anghel SI and Wahli W (2007) Fat poetry: a kingdom for PPAR gamma. Cell Res 17:486-511.
2. Baños G, Pérez-Torres I, and El Hafidi M (2008) Medicinal agents in the metabolic syndrome. Cardiovasc Hematol Agents Med Chem 6:237-252.
3. Bardot O, Aldridge TC, Latruffe N, and Green S (1993) PPAR-RXR heterodimer activates a peroxisome proliferator response element upstream of the bifunctional enzyme gene. Biochem Biophys Res Commun 192:37-45.
4. Bedu E, Wahli W, and Desvergne B (2005) Peroxisome proliferator-activated receptor beta/delta as a therapeutic target for metabolic diseases. Expert Opin Ther Targets 9:861-873.
5. Bensky D, Clavey S and Stöger E (2004) Chinese Herbal Medicine-Materia Medica, Eastland Press, Inc., Seattle, WA.
6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, and Bourne PE (2000) The Protein Data Bank. Nucleic Acids Res 28:235-242.
7. Chang F, Jaber LA, Berlie HD, and O'Connell MB (2007) Evolution of peroxisome proliferator-activated receptor agonists. Ann Pharmacother 41:973-983.
8. Cho N and Momose Y (2008) Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Curr Top Med Chem 8:1483-1507.
9. Choi SS, Cha BY, Lee YS, Yonezawa T, Teruya T, Nagai K, and Woo JT (2009) Magnolol enhances adipocyte differentiation and glucose uptake in 3T3-L1 cells. Life Sci 84:908-914
10. Desvergne B, Michalik L, and Wahli W (2006) Transcriptional regulation of metabolism. Physiol Rev 86:465-514.
11. Fruchart JC (2009) Peroxisome proliferator-activated receptor-alpha (PPARalpha): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 205:1-8.
12. Gregoire FM, Zhang F, Clarke HJ, Gustafson TA, Sears DD, Favelyukis S, Lenhard J, Rentzeperis D, Clemens LE, Mu Y, et al. (2009) MBX-102/JNJ39659100, a novel peroxisome proliferator-activated receptor-ligand with weak transactivation activity retains antidiabetic properties in the absence of weight gain and edema. Mol Endocrinol 23:975-988.
13. Gurnell M (2007) 'Striking the Right Balance' in Targeting PPARgamma in the Metabolic Syndrome: Novel Insights from Human Genetic Studies. PPAR Res 2007:83593.
14. Itoh T, Fairall L, Amin K, Inaba Y, Szanto A, Balint BL, Nagy L, Yamamoto K, and Schwabe JW (2008) Structural basis for the activation of PPARgamma by oxidized fatty acids. Nat Struct Mol Biol 15:924-931.
15. Lu IL, Huang CF, Peng YH, Lin YT, Hsieh HP, Chen CT, Lien TW, Lee HJ, Mahindroo N, Prakash E, et al. (2006) Structure-based drug design of a novel family of PPARγ partial agonists: virtual screening, x-ray crystallography, and in vitro/in vivo biological activities. J Med Chem 49:2703-2712.
16. Luquet S, Gaudel C, Holst D, Lopez-Soriano J, Jehl-Pietri C, Fredenrich A, and Grimaldi PA (2005) Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes. Biochim Biophys Acta 1740:313-317.
17. Markt P, Petersen RK, Flindt EN, Kristiansen K, Kirchmair J, Spitzer G, Distinto S, Schuster D, Wolber G, Laggner C, et al. (2008) Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modeling, 3D shape, and electrostatic similarity screening. J Med Chem 51:6303-6317.
18. Markt P, Schuster D, Kirchmair J, Laggner C, and Langer T (2007) Pharmacophore modeling and parallel screening for PPAR ligands. J Comput Aided Mol Des 21:575-590.
19. Marque FA, Simonelli F, Oliveira ARM, Gohr GL, and Leal PC (1998) Oxidative coupling of 4-substituted 2-methoxy phenols using methyltributylammonium permanganate in dichloromethane. Tetrahedron Lett 39:943-946.
20. Miyazawa M and Hisama M (2003) Antimutagenic activity of phenylpropanoids from clove (Syzygium aromaticum). J Agric Food Chem 51:6413-6422.
21. Murakami Y, Shoji M, Hanazawa S, Tanaka S, and Fujisawa S (2003) Preventive effect of bis-eugenol, a eugenol ortho dimer, on lipopolysaccharide- stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages. Biochem Pharmacol 66:1061-1066.
22. Newman DJ and Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461-477.
23. Ogata M, Hoshi M, Urano S, and Endo T (2000) Antioxidant activity of eugenol and related monomeric and dimeric compounds. Chem Pharm Bull 48:1467-1469.
24. Rachez C, Gamble M, Chang CP, Atkins GB, Lazar MA, and Freedman LP (2000) The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes. Mol Cell Biol 20:2718-2726.
25. Rizos CV, Elisaf MS, Mikhailidis DP, and Liberopoulos EN (2009) How safe is the use of thiazolidinediones in clinical practice? Expert Opin Drug Saf 8:15-32.
26. Rollinger JM, Steindl TM, Schuster D, Kirchmair J, Anrain K, Ellmerer EP, Langer T, Stuppner H, Wutzler P, and Schmidtke M (2008) Structure-based virtual screening for the discovery of natural inhibitors for human rhinovirus coat protein. J Med Chem 51:842-851.
27. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM, and Mortensen RM (1999) PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 4:611-617.
28. Sohn EJ, Kim CS, Kim YS, Jung DH, Jang DS, Lee YM, and Kim JS (2007) Effects of magnolol (5,5′-diallyl-2,2′-dihydroxybiphenyl) on diabetic nephropathy in type 2 diabetic Goto-Kakizaki rats. Life Sci 80:468-475.
29. Tenenbaum A, Fisman EZ, and Motro M (2003) Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2:4.
30. Wolber G, Dornhofer AA, and Langer T (2006) Efficient overlay of small organic molecules using 3D pharmacophores. J Comput Aided Mol Des 20:773-788.
31. Wolber G and Langer T (2001) Comb(i)Gen: a novel software package for the rapid generation of virtual combinatorial libraries, in Rational Approaches to Drug Design (Höltje HD, Sippl W ed) pp 390-399, Prous Science, Barcelona.
32. Wolber G and Langer T (2005) LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters. J Chem Inf Model 45:160-169.
33. Wright HM, Clish CB, Mikami T, Hauser S, Yanagi K, Hiramatsu R, Serhan CN, and Spiegelman BM (2000) A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem 275:1873-1877.
34. Yahara S, Nishiyori T, Kohda A, Nohara T, and Nishioka I (1991) Isolation and characterization of phenolic compounds from magnoliae cortex produced in China. Chem Pharm Bull 39:2024-2036.
35. Yu S and Reddy JK (2007) Transcription coactivators for peroxisome proliferator-activated receptors. Biochim Biophys Acta 1771:936-951.
36. Yumuk VD (2006) Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors. Ann NY Acad Sci 1083:306-318.