Text b. Pharmaceutical chemistry
PRE-READING TASK
1. Why did this direction of chemistry become a separate branch not so long ago compared to other directions?
2. What are the future perspectives of pharmaceutical chemistry: will it be beneficial to humanity or not?
Pharmaceutical chemistry and Medicinal chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where it is involved with design, chemical synthesis and development for market of pharmaceutical agents (drugs). Pharmaceutical chemistry encompasses drug design, drug synthesis, and the evaluation of drug efficacy (how effective it is in treating a condition) and drug safety. Prior to the nineteenth century, schools of pharmacy trained pharmacists and physicians how to prepare medicinal remedies from natural organic products or inorganic materials. Herbal medications and folk remedies dating back to ancient Egyptian, Greek, Roman, and Asian societies were administered without any knowledge of their biological mechanism of action. It was not until the early 1800s that scientists began extracting chemicals from plants with purported therapeutic properties to isolate the active components and identify them. By discovering and structurally characterizing compounds with medicinal activity, chemists are able to design new drugs with enhanced potency and decreased adverse side effects.
Drug discovery is the core of pharmaceutical chemistry. The drug discovery process includes all the stages of drug development, from targeting a disease or medical condition to toxicity studies in animals, or even, by some definitions, testing the drug on human subjects. Typically, conditions that affect a larger percentage of the population receive more attention and more research funding. Antiulcer drugs and cholesterol-reducing agents are currently the therapeutic areas of greatest emphasis. To develop a drug to target a specific disease, researchers try to understand the biological mechanism responsible for that condition. The biochemical pathways leading up to the disease being understood, scientists attempt to design drugs that will block one or several of the steps of the disease progress. Alternatively, drugs that boost the body's own defense mechanism may be appropriate.
Computers have transformed the drug discovery process. Rational drug design involves computer-assisted approaches to designing molecules with desired chemical properties. Molecular modeling software depicts three-dimensional images of a chemical which helps to demonstrate the size and shape of the drug, and the location of any charged groups. Chemists can vary the atoms or groups within the model and predict the effect the transformation has on the molecular properties of the drug. In this way, new compounds can be designed. Advances in technology have made it possible for medicinal chemists to synthesize a vast number of compounds in a relatively short time, a process referred to as combinatorial chemistry.
Every chemical that is synthesized must be tested for biological activity. In vitro testing involves biological assays outside a living system. New technologies have made it possible to assay large numbers of compounds in a short period. High-throughput drug screening allows pharmaceutical chemists to test between 1,000 and 100,000 chemicals in a single day! A compound that demonstrates some biological activity will undergo further tests, or it may be chemically modified to enhance its activity. Once a drug shows promise in vitro as a therapeutic agent, it must also be screened for toxic properties. To investigate drug toxicity, animal studies are performed. These studies also estimate mutagenicity, that is, whether the compound under investigation damages genetic material.
Scientists and government regulatory agencies having determined the drug candidate to be relatively safe, it can enter into clinical trials. The clinical stage involves four phases of testing on human volunteers. Phase I clinical trials evaluate drug tolerance and safety in a small group of healthy adult volunteers. Phase II trials continue to assess the drug safety and effectiveness in a larger population. Phase III and phase IV clinical trials involve even larger populations. During phase III trials, which can last two to eight years, a drug is often brought to market. Phase IV studies continue after the drug is being marketed.
The field of pharmaceutical chemistry is diverse and involves many areas of expertise. Natural-product and analytical chemists isolate and identify active components from plant and other natural sources. Theoretical chemists construct molecular models of existing drugs to evaluate their properties.
WHAT DO PHARMACEUTICAL CHEMISTS DO?
Scientists in pharmaceutical chemistry are principally industrial scientists, working as part of an interdisciplinary team that uses their chemistry abilities, especially their synthetic abilities, to use chemical principles to design effective therapeutic agents. Their work involves chemical aspects of identification, and then systematic, thorough synthetic alteration of new chemical entities to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their structure-activity relationships (SAR). Pharmaceutical chemists are focused on quality aspects of medicines and aim to assure fitness for purpose of medicinal products.
Graduate level programs in pharmaceutical chemistry can be found in traditional medicinal chemistry or pharmaceutical sciences departments, both of which are traditionally associated with schools of pharmacy, and in some chemistry departments. Most entry-level workers in pharmaceutical chemistry do not have formal training but receive the necessary pharmaceutical and pharmacologic background after employment—at entry into their work in a pharmaceutical company, where the company provides its particular understanding or model of training through active involvement in practical synthesis on therapeutic projects.
Speak on the history of pharmaceutical chemistry.
Dwell on the main stages of drug design and testing.
Specify the main areas of activity for pharmaceutical chemists.
Comprehension check????
Exercise 1.
Match the following words on the left with the appropriate synonyms on the right:
remedy |
a route or a course |
to administer |
unfavorable consequences |
to purport |
intensified power |
enhanced potency |
to imply or claim to be |
adverse effects |
to apply or dispense |
pathway |
medication or cure |
Exercise 2.
Some of the following sentences can be incorrect. Find the mistakes and correct them.
In early times schools of pharmacy trained people how to prepare medicinal remedies only from natural organic products.
Knowing structural characteristics of compounds with medicinal activity, chemists are able to design new drugs with better properties and fewer adverse side effects.
To develop a drug to target a specific disease, researchers try to understand the possible adverse effects of this drug that can be responsible for that condition.
Every chemical that is synthesized must be tested in vitro and in vivo.
Most entry-level workers in pharmaceutical chemistry shouldn’t have any training and have no necessary pharmaceutical and pharmacologic background after employment.
Exercise 3.
Complete the following passage using the words from the box.
preparations, adverse, compounds, side effects, potent, biological activity, combating, therapeutic agents, lead, remedy |
How do chemists "discover" drugs? Often there is an existing (1) … for a condition, and scientists will evaluate how that drug exerts its actions. Once the drug's structure is known, the drug can serve as a prototype or "lead compound" for designing more effective (2) … of similar chemical structure. (3) … compounds are molecules that have some (4) … with respect to the condition under investigation. However, the lead compound may not be effective in (5) … the disease, or it may produce undesirable (6) …. Lead optimization involves chemical modifications to the lead compound to produce a more (7) … drug, or one with fewer or decreased (8) … effects. Compounds used as medicines are most often organic (9) …, which are often divided into the broad classes of small organic molecules (e.g., atorvastatin, clopidogrel) and "biologics” (erythropoietin, insulin glargine), the latter of which are most often medicinal (10) …. of proteins (natural and recombinant antibodies, hormones, etc.). Inorganic and organometallic compounds are also useful as drugs (e.g., lithium and platinum-based agents such as lithium carbonate)