Scribd
Upload
32 views5 pages

Advanced Approaches in Drug Design and Development

Uploaded by

Hassan kamal
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
32 views5 pages

Advanced Approaches in Drug Design and Development

Uploaded by

Hassan kamal
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 5

Drug Design & Recent Approaches

Drug:
A chemical compound used in the diagnosis, treatment, or prevention of disease or other
abnormal condition.
Or
Compounds used for the prevention and treatment of diseases like cancer, etc.
Drug design

Drug design is the inventive process of finding new medications based on the knowledge of the
biological targets.

Drug design aims at developing a drug with high degree of therapeutic index and specific action.
The ‘drug design’ in a broader sense implies random evaluation of synthetic as well as natural
Products. It involves creation of newer drug molecules based on biologically-active compounds
derived from either plant or animal kingdom, synthesis of their derivatives displaying improved
biological actions, and finally precise design of a drug that is enable to interact with a receptor site
efficaciously.
Purpose of drug design:
1. To examine the effects of biological compounds on the basis of molecular interaction.
2. To understand various processes by which the drugs usually produce their pharmacological
effects.
3. How the drugs specifically react with its particular receptor to produce a particular
pharmacological response.
4. How the drugs usually get modified or detoxicated, metabolized or eliminated by the
organism.
Ideal drug:
 Target specific, the drug should specifically interact to its particular target.
 Ease of administration, produce no irritation when administered through different route of
administration Oral, IV, IM etc.
 No drug interaction
 Low cost
Need of new Drug:
1. New diseases are being discovered day by day, therefore in order to cure these newer
diseases, there is a need to design new drugs.
2. The therapeutic efficacy of the drugs are low, thus to enhance the efficacy, new drugs are
designed.
3. To overcome the side effects of the drugs and the cost of therapy.
4. To sustain industrial activity (pharmaceutical industry needs to make new drugs or
continue their research in order to compete with other industries).
Conventional drug design and development methodologies:

Old methods to discover drugs

Serendipitous drug discovery:

‘’Serendipity” in drug discovery implies the finding of one thing while looking for something else.

Examples:

1. The serendipitous discovery of penicillin in 1928 by Alexander Fleming.

2. Phenolphthalein was considered as a useful dye for cheap wines; after a heroic self-
experiment, a pharmacologist experienced its drastic diarrheic activity.

3. Warfarin was used as a rat poison.

4. The vaso-dilatory activity of amyl nitrite and nitroglycerin was discovered by chemists
who developed strong headaches after inhaling or ingesting minor amounts.

Mechanism-Based Drug design


 In this method, complete pathway of a disease is studied and the receptor targets are
selected from that diseased mechanism and a new drug is designed that interacts with that
target and produces the desired action.

Different approaches in drug design and development:

Traditional Drug designing methodologies are:

1. challenging
2. Expensive
3. Time consuming

So, Multidisciplinary approach:

Computational tools along with advanced computational methodologies for structure guided
approaches such as Molecular docking, Pharmacophore modeling, 3D-QSAR by many software
can be applied to:

1. Enhance efficacy of drug


2. Reduce cost of drug design.
3. Save time.
4. Understand drug ligand interaction mechanism.

The modern drug discovery processes or drug design

Computer aided drug design (CADD)

 Ligand based drug design, i.e. Pharmacophore modeling, 3D-QSAR.


 Structure based drug design, i.e. Molecular Docking, Structure based Pharmacophore
modeling.

Pharmacophore modeling:

A pharmacophore is an abstract description of molecular features that are necessary for molecular
recognition of a ligand by a biological macromolecule.

Information obtained from Pharmacophore model:

 Defines the important groups involved in binding.


 Defines the relative positions of the binding groups.

 Gives sufficient information about active conformation of drug compounds.

 Important to drug design and discovery.

Model development:

1. Select a training set of ligands: Choose a structurally diverse set of molecules that will be
used for developing the pharmacophore model. The set of molecules should include both
active and inactive compounds.
2. Conformational analysis: minimize energy to obtain biologically active conformation of
selected molecules.
3. Molecular superimposition: Superimpose ("fit") all combinations of the low-energy
conformations of the molecules.
4. Abstraction: Transform the superimposed molecules into an abstract representation. For
example, superimposed phenyl rings might be referred to more conceptually as an
'aromatic ring' pharmacophore element.
5. Validation: A pharmacophore model is a hypothesis accounting for the observed
biological activities of a set of molecules that bind to a common biological target.
3D-QSAR modeling: Model development:

3D-QSAR stands for three-dimensional quantitative


structure activity relationship and is one of the most
extensively used technique among all Computational
Aided Drug Design (CAAD) techniques.
Molecular Docking:
Docking is the process of predicting the stable three-
dimensional structure of a bound pair of molecules i.e. binding
pose of ligand in active site of its receptor.
Molecular docking steps:

Application of CADD:

1. Helps to identify the active site in particular target.


2. Helps to uncover the kinetic basis of ligand selectivity for specific target.
3. Helps to identify the structural determinants for inhibition of specific protein.
4. Allows to investigate the contribution of chemical features of receptor and electrostatic
features of ligands to their selectivity.
5. Allows us to predict the relative binding affinities of ligands to their respective target.
6. We can identify active site residues, responsible for selective ligand-protein binding.
7. Gives us a model for further design of isoform specific inhibitors.

You might also like

pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy