DISCIPLINE OF PHARMACEUTICAL CHEMISTRY
DRUG DESIGN AND DISCOVERY
A drug is a substance that we used mostly in our daily lives. It is a chemical substance with physiological effects when ingested or introduced into our bodies. The response produce can either be beneficial or harmful. Toxins and poisons can be classified as drugs. This report the term ‘drug’ is for medicinal or pharmaceutical purposes. Drugs used to prevent or treat diseases. Drug design also known as rational drug design is the creative process of discovering or finding a new drug based on the knowledge of a biological target. Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinity, selectivity (to reduce the potential of side effects), efficacy/potency, metabolic stability (to increase the half-life), and oral bioavailability. Once a compound that fulfils all of these requirements has been identified, it will begin the process of drug development prior to clinical trials. One or more of these steps may, but not necessarily, involve computer-aided drug design.
Humanity has been has been consuming and experimenting with drug substance for centuries. This dates back in the early days of human civilization when drugs were not only used for their therapeutic properties but they were also used in association with religion and spiritual healing. This all changed when chemistry reached a high level of maturity principles and methods started to be applied and drug researches were performed this then gave rise to drug discovery and design. In the 1800s drug design and discovery started following scientific techniques and around the 1810 essential foundations of chemical theory had been laid. Drugs are mostly discovered by accident or by “luck”. Drug discovery deals with the synthesis and design of the drug. It is not the drug itself that that gets discovered but the active ingredient of the lead component. Lead compound discovery is the starting point of drug discovery and design. It can be discovered from various sources either natural for example venom from animals or plant flora. The lead compound can consist of desirable characteristics and of undesirable characteristics such as decrease in metabolism, toxicity, heart problems etc. The lead compound can be modified to enhance their desired effects and to eliminate or reduce the undesirable effects.
In this report will be discussing the drug design and discovery process in details and the analytical techniques used in small molecule drugs. Small molecule drugs refer to drugs with small molecular weight of less than 1000 daltons, between 300 to 7000 daltons to be exact.
6. ANALYTICAL TECHNIQUES USED IN DDD
6.1 X-ray crystallography
X-ray crystallography uses x-ray on crystals. X-rays are electromagnetic waves with a short wavelength of 0.01-100 nm. This helps because the atomic structures have bond lengths of 0.1-0.2 nm, thus able to resolve atomic details. This method determines atomic and molecular structure of crystals. It is used in drug design and discovery as a standard technique for three dimensional structures. It is the only method that determines the absolute configuration of a molecule. The drug compound of protein molecules to be studied using an x-ray, must be in crystalline form. This allows the compound or the molecules are orderly arranged in building blocks containing a molecule protein. This then form imaginary cubes termed unit cell. (Figure 6.1.1)
Figure 6.1.1: Crystalline molecules in 3D (Unit cells)
X-ray beams are the focused on different of these unit cells, a 3D diffraction pattern is created consisting of many diffraction spots. Each diffraction spot has an intensity which is the summation of constructive interference by the atoms in the molecule at a certain orientation, and the dimensions and pattern are due to the geometric...
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