Subscribe to RSS
DOI: 10.1055/s-2007-990216
© Georg Thieme Verlag KG Stuttgart · New York
Reverse Pharmacognosy: Identifying Biological Properties for Plants by Means of their Molecule Constituents: Application to Meranzin
Publication History
Received: June 22, 2007
Revised: July 16, 2007
Accepted: July 19, 2007
Publication Date:
13 September 2007 (online)
![](https://www.thieme-connect.de/media/plantamedica/200712/lookinside/thumbnails/10.1055-s-2007-990216-1.jpg)
Abstract
Reverse pharmacognosy aims at finding biological targets for natural compounds by virtual or real screening and identifying natural resources that contain the active molecules. We report herein a study focused on the identification of biological properties of meranzin, a major component isolated from Limnocitrus littoralis (Miq.) Swingle. Selnergy™, an in silico biological profiling software, was used to identify putative binding targets of meranzin. Among the 400 screened proteins, 3 targets were selected: COX1, COX2 and PPARγ. Binding tests were realised for these 3 protein candidates, as well as two negative controls. The predictions made by Selnergy were consistent with the experimental results, meaning that these 3 targets can be modulated by an extract containing this compound in a suitable concentration. These results demonstrate that reverse pharmacognosy and its inverse docking component is a powerful tool to identify biological properties for natural molecules and hence for plants containing these compounds.
Key words
Inverse docking - Limnocitrus littoralis - Rutaceae - cyclooxygenase - meranzin - Selnergy - reverse pharmacognosy
- Supporting Information for this article is available online at
- Supporting Information .
References
- 1 Bruneton J. Pharmacognosie, Phytochimie, Plantes Médicinales. Paris; Lavoisier 1993: viii.
- 2 Do Q T, Bernard P. Pharmacognosy and reverse pharmacognosy : a new concept for accelerating natural drug discovery. IDrugs. 2004; 7 1017-27.
- 3 Harrigan G G, Brackett D J, Boros L G. Medicinal chemistry, metabolic profiling and drug target discovery: a role for metabolic profiling in reverse pharmacology and chemical genetics. Mini Rev Med Chem. 2005; 5 13-20.
- 4 Shoichet B K, Stroud R M, Santi D V, Kuntz I D, Perry K M. Structure-based discovery of inhibitors of thymidylate synthase. Science.. 1993; 259 1445-50.
- 5 Rollinger J M, Haupt S, Stuppner H, Langer T. Combining ethnopharmacology and virtual screening for lead structure discovery: COX-inhibitors as application example. J Chem Inf Comput Sci. 2004; 44 480-8.
- 6 Liu H, Li Y, Song M, Tan X, Cheng F, Zheng S. et al . Structure-based discovery of potassium channel blockers from natural products: virtual screening and electrophysiological assay testing. Chem Biol. 2003; 10 1103-13.
- 7 Bernard P, Scior T, Didier B, Hibert M, Berthon J Y. Ethnopharmacology and bioinformatic combination for leads discovery: application to phospholipase A(2) inhibitors. Phytochemistry. 2001; 58 865-74.
- 8 Chen Y Z, Zhi D G. Ligand-protein inverse docking and its potential use in the computer search of protein targets of a small molecule. Proteins. 2001; 43 217-26.
- 9 Paul N, Kellenberger E, Bret G, Muller P, Rognan D. Recovering the true targets of specific ligands by virtual screening of the protein data bank. Proteins. 2004; 54 671-80.
- 10 Do Q T, Renimel I, Andre P, Lugnier C, Muller C D, Bernard P. Reverse pharmacognosy: application of selnergy, a new tool for lead discovery. The example of epsilon-viniferin. Curr Drug Discov Technol. 2005; 2 161-7.
-
11 Tripos Inc 1699 South Hanley Rd.; St. Louis, Missouri, 63 144, USA.;
- 12 Berman H M, Westbrook J, Feng Z, Gilliland G, Bhat T N, Weissig H. et al . The protein data bank. Nucleic Acids Res. 2000; 28 235-42.
- 13 Rarey M, Kramer B, Lengauer T, Klebe G. A fast flexible docking method using an incremental construction algorithm. J Mol Biol. 1996; 261 470-89.
- 14 Pearlman R S. CONCORD® 4.0.7A, ”Concord User's Manual,”. distributed by Tripos Inc St. Louis, MO.;
- 15 Press W H, Flannery B P, Teukolsky S A, Vetterling W T. Simplex. Numerical recipes in C, the art of scientific computing. Cambridge; University Press 1988: 312-27.
- 16 Powell M JD. An efficient method for finding the minimum of a function of several variables without calculating derivatives. Comp J. 1964; 7 155-62.
-
17 Maclouf J, Grassi J, Pradelles P. Development of enzyme-immunoassay techniques for the measurement of eicosanoids. In: Walden TL, Hughes HN; editors
Prostaglandin and lipid metabolism in radiation injury . New York; Plenum Press 1987: 355-64. - 18 Bieth J, Spiess B, Wermuth C G. The synthesis and analytical use of a highly sensitive and convenient substrate of elastase. Biochem Med. 1974; 11 350-7.
- 19 Gilde A J, van der Lee K A, Willemsen P H, Chinetti G, van der Leij F R, van der Vusse G J. et al . Peroxisome proliferator-activated receptor (PPAR) alpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res. 2003; 92 518-24.
- 20 Garavito R M, Picot D, Loll P J. Preliminary X-ray investigations into NSAID-binding to cyclooxygenase-1. Am J Ther. 1995; 2 611-5.
- 21 Gierse J K, McDonald J J, Hauser S D, Rangwala S H, Koboldt C M, Seibert K. A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors. J Biol Chem. 1996; 271 15 810-4.
- 22 Xu H E, Lambert M H, Montana V G, Plunket K D, Moore L B, Collins J L. et al . Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A. 2001; 98 13 919-24.
- 23 Zanotti G, Berni R. Plasma retinol-binding protein: structure and interactions with retinol, retinoids, and transthyretin. Vitam Horm. 2004; 69 271-95.
- 24 Zoraghi R, Corbin J D, Francis S H. Phosphodiesterase-5 Gln817 is critical for cGMP, vardenafil, or sildenafil affinity: its orientation impacts cGMP but not cAMP affinity. J Biol Chem. 2006; 281 5553-8.
- 25 Mattos C, Rasmussen B, Ding X, Petsko G A, Ringe D. Analogous inhibitors of elastase do not always bind analogously. Nat Struct Biol. 1994; 1 55-8.
- 26 Fiorucci S, Meli R, Bucci M, Cirino G. Dual inhibitors of cyclooxygenase and 5-lipoxygenase. A new avenue in anti-inflammatory therapy? Biochem Pharmacol. 2001; 62 1433-8.
- 27 Hito C, Furukawa H. Constituents of Murraya exotica L. Structure elucidation of new coumarins. Chem Pharm Bull. 1987; 35 4277-85.
Dr Philippe Bernard
GREENPHARMA S. A.
3 allée du Titane
45100 Orléans
France
Phone: +33-2-3825-9980
Fax: +33-2-3825-9965
Email: philippe.bernard@greenpharma.com
- www.thieme-connect.de/ejournals/toc/plantamedica