Design and Materials
Farahsyifa Mutiara Khansa
Khaula Muhammad Rausyan Fikri
Rizki Ihza P.
Designing New Medicinal Drugs
• What we need to know ?
• Identify the structural features of the active site for particular enzyme associated with the pathogen.
• Determine the functional groups present to ensure effective binding of the drug. • Intermolecular bonds of drugs-activesite :
• Hydrogen bond
• Ionic attraction
• Dipole-dipole forces
• Van der Waals’ forces
Computerized Molecular Modelling
• Molecular modelling greatly speeded up the process of designing new medicines by eliminating the needs of conventional methods (trial and error). • By using molecular modelling, only molecules that fit with the active sites’ of the target are made and undergo clinical test.
• Molecular modelling also used to design many other compounds like pesticides and polymers with specific characteristics.
A Brief History of HIV-AIDS
• Early on 1988 X-Ray Crystallography were used to
determine the shape of HIV protease.
• Discovery of a molecule that block its active site is a
one step to the cure.
• By imitating the molecule (substrate) that the enzyme
worked on, inhibitors were made using molecular
• In less than 8 years pharmaceutical companies
developed three new anti-viral drugs for HIV.
• HIV mutated and became resistant to the drugs
• Scientists develops new drug to inhibit mutant HIV.
A Symmetrical HIV protease molecule
• Most drugs contain at least one chiral
• Chiral centre is a carbon atom bonded to
four different atoms or groups of atoms
and exists as mirror images.
• These isomers cause by Chiral centre are
called enantiomers and optically active.
• They differ in the ability to rotate the
plane of polarized light.
Chirality in pharmaceutical
• Using conventional reactions will yield 50:50 mixture of the enantiomers (racemic mixture).
• They differs in their “pharmaceutical activity”.
• i.e. naproxen is used to treat arthritis while its other enantiomer will cause liver damage.
• About 80% patented drugs are single enantiomers.
Benefits of pure enantiomers
• Reduce patient’s dosage as it is more potent, cutting costs and minimizing the risk of side-effects.
• Protects drugs companies from sues as people suffer damage from sideeffects. • Three ways to prepare pure enantiomers:
• Optical resolution
• Using optically active starting materials
• Using chiral catalyst.
• Optical resolution is the Separation of racemic mixture. • Using a pure enantiomer of another optically active compound (called a chiral auxiliary) that react with one of the isomers.
• The new formed product will have different properties and can be separated by physical means.
• i.e. the unwanted enantiomer and the new product can be separated by fractional crystallization then the new product converted back to the desired enantiomer by adding dilute alkali.
• Bad sides of Optical Resolution
• This method is repeated many times to ensure purity.
• It is difficult, time-consuming, uses extra reagents and involves disposal of the other half of the racemic mixture.
• Using large volumes of organic solvents that oftenly
harmful to environment.
• Supercritical carbon dioxide is used as a solvent which
is much safer. CO2 @ 31 Celsius and 73 atm.
Optically Active Materials
• Using starting materials that are optically active and in the same orientation as the desired product.
• Naturally occurring compounds such as carbohydrates or L-Amino Acids. • This route is to keep any intermediates and end products formed in the same enantiomer form.
• No need to carry further separation of racemic mixtures and cheaper costs.
Catalysts that ensure only one specific enantiomer is formed. Needed in small quantities and can be...
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