Chapter 10 Manipulating Molecules and Designing Drugs Is our society becoming dependent on prescription drugs? ow harmful are illicit drugs? ow are effective drugs designed? erbal remedies: Is natural safer than synthetic?
A wonder drug? The classic white willow tree, Salix alba, provides more than just shade and shelter for natures animals. Salicin is the key ingredient that is isolated from the tree and converted into one of our most reliable and heavily used drugs, aspirin! It is used as an antipyretic-fever reduction. White willow tree It is used as an analgesic-pain reliever, and as an anti-inflammatory agent. salicyn 10.1
Semi-synthesis of aspirin: from natural product to marketed drug Salicylic acid acetic acid anhydride acetylsalicylic acid (aspirin) acetic acid White willow tree Possible side effects: 1. eartburn 2. Nausea 3. Reye s Syndrom 4. Ringing in ears 5. Rash, itch 6. Shortness of breath Would this drug make it through FDA scrutiny today? 10.1
Organic Chemistry The Study of Carbon Compounds There are over 12 million known organic compounds. Why carbon? Carbon has the remarkable ability to bond in multiple ways: 10.2
Some different ways to represent molecular structures: Structural formula Ball-and-stick formula Space-filling model 10.2
Representing molecular structures with line-angle drawings: C C C C C C = iso hexane, or 2-methyl pentane C C C C C cyclopentane = Each vertex (or end of a line) represents a carbon with an appropriate number of hydrogen atoms. 10.2
10.2
Representations of benzene (C 6 6 ), an important part of many drug molecules. 10.2
Functional groups - arrangements of groups of atoms which impart characteristic physical and chemical properties. 10.3
More Important Functional groups The presence and orientation of functional groups are responsible for the action of all drugs. See Chapter 9 for more info on functional groups. 10.3
Ester Formation O This O and this form 2 O O C O O O C O C 3 C O O C O + O this O attaches here Ester functional groups are often found in drugs, flavorings, and fragrances. C 3 10.3
What are the functional groups in the aspirin molecule? 1. Benzene ring 2. Carboxylic acid 3. Ester 10.3
Salt Formation O C 3 C C C 3 N + Cl O C 3 C 3 C C N 2 Cl - Pseudoephedrine freebase Pseudoephedrine hydrochloride The salt forms are often preferred as drugs: Increased water solubility No odor igher melting points (longer shelf life) 10.3
Examples of polar molecules Functional groups may impart a polar aspect to a molecule. A polar molecule has partial charge separation. d - = partial negative d + = partial positive 10.3
ormones, our chemical messengers, are produced by the body s endocrine glands. ormones encompass a wide range of functions and a similarly wide range of chemical composition and structure. Enzymes are proteins that act as biochemical catalysts, influencing the rates of chemical reactions. Aspirin works by inhibiting the production of certain enzymes responsible for producing specific hormones. 10.4
Drugs may be broadly classified as: 1. Those that cause a physiological response in the body. aspirin anticancer drugs morphine 2. Those that kill foreign invading organisms. antibiotics antifungal agents 10.4
Aspirin, revisited mode of action COX enzymes Prostaglandin production COX -1: liver function, stomach lining COX-2: fever, pain sensation, inflammation 10.4
Drug Discovery-serendipity Sir Alexander Fleming, British bacteriologist Working with Staphylococcus-a bacteria. A colleague working in same building was working with Penicillium notatum-a fungus that produces penicillin. Actual photo of petri dish Flemming showing inhibition of growth of bacteria where penicillin landed on the dish. Series of chance occurrences, and penicillin was discovered. 10.5
Drug Discovery-serendipity O N S C 3 PhOC 2 O Penicillin V N C 3 COO In the fields of observation, chance favors only the prepared mind -Louis Pasteur ow many functional groups can you identify in the structure above? 10.5
Drug interactions at the cellular level The lock and key model. A substrate is a substance whose reactions are catalyzed by an enzyme. ere you see a drug occupying the receptor site of the natural substrate. 10.5
The functional groups and their placement in three-dimensional space determines to a large degree a molecule s biological activity. The portion of a molecule that determines the biological effects of a drug is called the pharmacophore. 10.5