Reverse pharmacognosy
- 2. It is a new concept that accelerates the Natural Drug Discovery New Drug Development-long-costly –process High Throughpuorial t methods like Combinatorial chem,HTS Invitro Active selective Hits Invivo Active??????????? New Approach Reverse Pharmacog coupled with Pharmacog
- 3. RP uses HTS Virtual screening Knowledge Data base(traditional usage of plants)
- 5. Pharmacognosy and reverse pharmacognosy. Pharmacognosy: Plants are selected by means of ethnopharmacological knowledge, taxonomic biotope diversity coupled with in-house “patentability” criteria, then extracts are made and tested. Bio- guided characterization is undertaken for extracts of interest to isolate bio-active molecule(s). Reverse pharmacognosy: Natural compounds are selected by in- house druglikeness and chemical diversity criteria. They are submitted to Selnergy™ for prediction of activity then validated in biological tests, or the molecules are evaluated directly in biological assays. The last step consists in using our internal knowledge database(ETPHDB) to identify the source(s) of the validated compounds.
- 6. Has FIVE components Virtual Screening Tools Target Database 3D Structural database of natural compounds Natural compound library Ethenopharmacological database
- 7. Virtual chemical database Contains 100,000 molecules or natural compounds Subset extraction based on Lipinski rules or derived criteria
- 8. Target database Has protein 3D structures determined by X-ray crystallography or inhouse homology models. Each of them has internal codes (PDB code). Data recording for virtual screening tools is done. RMSD Interaction energy Co-crystallised ligand position
- 9. Selenergy (Selectivity+Synergy) Virtual HTS tool with inputs – VCDB, Target database Selectivity of ligand to the target is measured Synergy- ligand binds to target or other targets
- 11. Ethnopharmacological database Has ethnobotanical data
- 12. RP has two parts 1. Experimentation 2. In silico dependent initial step
- 13. In silico VCDB Compound selection (Ex: Drug) Compound selection based on Feher & Schmidt Subset Sent to target database (priorly target selection done) Selenergy Docking score, RMSD ETPHDB Compound source
- 14. Experimentation Source Compounds isolated HTS or In vitro screening In vivo screening Real hit
- 17. Schema of reverse pharmacognosy. Line arrows represent information flow and 3-D arrows correspond to process flow. There are two parts in reverse pharmacognosy: one is experimental and the other relies on in silico tools in the initial steps. Data from ethnopharmacological database (ETPHDB) are utilized for “knowledge validation” in virtual to real hits and to retrieve the sources of compounds. Experimental validation process consists in internal biological tests and/or data gathered in scientific literature. Real hits or real inactive candidates are interesting for the refinement of our target models. VCDB and target DB are the input for Selnergy.
- 18. Selnergy™ module. Selnergy™ is a proprietary tool developed by Greenpharma for biological profiling, able to analyze synergy and selectivity for a set of compounds vs. several biological targets. It couples an in-house target library, a worldwide standard docking program and an analysis module. The target library includes more than 1500 protein structures from crystallography and homology models. They are classified according to their experimental origin, their source, the therapeutic class and protein class. This module is adequate for bio-focused libraries. For example, the development of a reduced library of compounds with potential anti-inflammatory activity. All targets involved in inflammatory diseases will be screened.
- 20. Ethnopharmacological database (ETPHDB) contains botanical information on plants, traditional usage and phytochemistry data associated with biological activity information. So it is straightforward to link plants/molecules/activity.