Traditional Drug design vs Rational Drug design.pptx

traditional vs rational drug delivery design

1. TRADITIONAL DRUG DESIGN VS RATIONAL DRUG DESIGN SAHANA B.H DEPARTMENT OF PHARMACOLOGY

2. Traditional Drug Designing Traditional drug discovery involves the origin of drug discovery that evolved in natural sources, accidental events etc. It was not target based and not much systemised as today. Improvement and advancement in pharmaceutical science and technology made it evolutionised to much more systemised modern drug discovery.

3. Methods of Traditional drug design Random Screening Trial & Error Method. EthnoPharmacology Approach. Serendipity Method. Classical Pharmacology

4. Random Screening It includes random screening of synthetic compounds/chemicals/natural products by bioassay procedures. It involves two approaches: Screening of selected class of compounds like alkaloids, flavonoids etc. Screening of randomly selected plants. CDRI of CSIR of India screened almost 2000 plants for biological efficacy with random screening.

5. 2. Trial & Error Method Trial and error includes berries, roots, leaves and barks that could be used for medicinal purposes. Examples: Cinchona Bark contains quinine used to reduce fever in malaria. Leaves of Azadirachta indica (Neem) are used as anti-inflammatory and antibacterial properties etc. Licorice roots are traditionally used to treat stomach ulcers, bronchitis and sore throats.

6. 3. Ethnopharmacology approach Ethnopharmacology is the study of medicinal plants used in specific cultural groups. It involves the observation, description, and experimental investigation of indigenous drugs. It is based on botany, chemistry, biochemistry, pharmacology and many other disciplines like anthropology, archeology , and history. Andrographis paniculata ( Kalmegh ) was used for dysentery in ethnomedicine and the compounds responsible for the activity were found to be andrographolides.

7. 4. Serendipity Method "Serendipity" refers to 'an accidental discovery' i.e , 'finding one thing while looking for something else’ The most important example of this method is the discovery of Penicillin by Alexander Fleming in 1928 while doing research on influenza. One more example is the discovery of Cisplatin (used in bladder cancer) while studying E.coli bacteria .

8. 5. Classical Pharmacology Also known as Function based approach. Without the prior identification of drug target. Anciently, drug discovery processes were often based on measuring a complex response in-vivo such as Prevention of experimentally induced seizures Lowering of blood sugar Suppression of inflammatory response Example: Discovery of Foxglove in Europe

9. Rational Drug Design It is the process in which finding of new medication based on knowledge of biological target is done. It involve design of small molecular that are complementary in shape and charge to biomolecular target. The drug is most commonly an organic small molecule that activate/inhibit the function of biomolecule such as protein which in turn result in therapeutic benefit of patient.

10. Rational drug design can broadly divided into two categories: Development of molecule with desired properties for target having known structure and function. Development of molecule with predefined properties for target whose structural information may be or may not be known. The unknown target identification can be found by global gene expression data.

11. Types of Rational Drug Designing Method 1] Ligand Based Drug Designing QSAR Pharmacophore Perception 2] Structure Based Drug Designing Docking De novo Drug Design

12. 1] Ligand Based Drug Design It relies on the knowledge of other molecules that bind to the biological target of interest. In other words, a model of the biological target may be built based on the knowledge of what binds to it and this model in turn may be used to design new molecules. In QSAR, biological activity is determined from the physico -chemical properties of drug. So these QSAR relationships in turn used in the prediction of biological activity of new analogues. Biological Activity=f( physico -chemical properties)

13. b) Pharmacophore - based Drug Design Examine features of inactive small molecules (ligands) and the features of active small molecules (ligands) Generate a hypothesis about what chemical groups on the ligand are necessary for biological function; what chemical groups suppress biological function. Generate new ligands which have the same necessary chemical groups in the same 3D location.

14. 2] Structure Based Drug Design It relies on the knowledge of 3D structure of the biological target. 3D structure is obtained by either X-Ray crystallography or NMR spectroscopy. Using the structure of receptor, candidate drugs that are predicted to bind with high affinity and selectivity to the target may be designed.

15. Molecular Docking It is a computational method to predict the interaction of two molecule generation a binding model. Docking is done between a small molecule and a macromolecule. It is the study of how two or more molecular structures fit together. It is an attempt to find best matching between two molecules. Types of docking: Rigid Docking Flexible Docking Manual Docking

16. b) De novo Drug Design It is the process in which 3D structure of receptor is used to design newer molecules. It involves structural determination of the lead target complexes and lead modifications using molecular modeling tools. Information available about target receptor but no existing leads that can interact. Types of De novo Drug Design a) Atom based construction b) Fragment based construction

17. REFERENCE: Silverman RB, Holladay MW. The organic chemistry of drug design and drug action. 3rd ed. Academic Press; 2014. Patrick GL. An introduction to medicinal chemistry. 6th ed. Oxford University Press; 2017. Ghosh D, Chattaraj PK. Rational drug design: Basics and applications. J Mol Model. 2020;26(6):135. Bajorath J. Computational approaches in medicinal chemistry: Current applications and future perspectives. Future Med Chem. 2014;6(5):515-7. López-Vallejo F, Caulfield T, Martínez-Mayorga K, Giulianotti MA, Nefzi A, Houghten RA, et al. Integrating virtual screening and combinatorial chemistry for accelerated drug discovery. Comb Chem High Throughput Screen. 2011;14(6):475-87.