Rajnarayanan_APR092015_PMY311_upload - CHEMICAL STRUCTURE...

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CHEMICAL STRUCTURE
DRUG DISCOVERY Raj Rajnarayanan, Ph.D., Pharmacology & Toxicology PMY311 Chemistry of Drug Action
INTEGRATED INFORMATICS
This is the first time that all the atoms in a molecule have been imaged,‘ - Single molecule, one million times smaller than a grain of sand, pictured for first time IBM researchers Nikolaj Moll, Reto Schlittler, Gerhard Meyer, Fabian Mohn and Leo Gross [OCT 2009]
HDAC-SAHA STRUCTURE & LIGAND BASED DRUG DISCOVERY
Sources of Drugs Drugs originate from plants (25%), animals (6%), microorganisms (12%), minerals (7%), and from synthesis in the medicinal chemistry laboratory (50%). 1. Plants Plants produce a variety of physiologically active substances. The study of plants that produce drugs is called pharmacognosy. The most common types of drugs produced by plants are called alkaloids. Approximately 30 alkaloids are in use as drugs. Examples of alkaloids are codeine, colchicine, reserpine, ephedrine, quinine, atropine and quinidine. Other drugs produced by plants are the cardiac glycosides (steroidal sugars) such as digoxin, the purines such as theophylline used to treat asthma, and taxol, an anticancer drug originally obtained from the bark of the pacific yew tree.
Alkaloids are biologically active basic, tertiary amine-containing, organic compounds of generally complex structure. Different alkaloids may be produced in different parts of plants, e.g. roots, leaves seeds, etc. Alkaloids are poorly soluble in water and their water solutions are alkaline (see equation below). Alkaloids react with mineral acids (HCl, H2SO4, HNO3, etc.) to form salts that are generally very water soluble. Salts may be recovered from aqueous solution by evaporation of water. Morphine is obtained from opium, which is the sun-dried latex of the unripe fruit of the poppy plant, Papaver somniferum. Of the approximately 25 alkaloids in opium, morphine is the most important. Codeine is a methylated derivative of morphine (on the phenolic-OH at the 3- position) and it constitutes about 1-2% of opium.
2. Animals A liter of urine from pregnant mares yields 10 mg of estrone. A mixture of estrogens (primarily estrone) is used as a post-menopausal estrogen therapy: Wyeth-Ayerst Drug Company markets this as Premarin, the name being derived from pre gnant mar es u rin e . Fat soluble vitamins A and D can be obtained from fish liver oil. These vitamins play a role in night vision and bone development, respectively.