Atropine.pptx

Atropine

1. Natural Products as Source of Potential Drugs and Systematic Compounds By Muhammad Rashad PhD Pharmaceutical Chemistry Natural Product Chemistry

2. The term natural product refers to any naturally occurring substance, generally a secondary metabolite; small molecule that is not involved in the main life processes. Natural products isolated from various sources especially derived from plants, have long been used in treatment of human ailments. For long time, the approach to new drugs through natural products was proved to be the single most successful strategy for the discovery of new drugs. Introduction

3. Atropine Atropine is anticholinergic drug obtained from tropane alkaloid. It is racemic mixture of equal parts of d and l-hyoscyamine but activity of atropine is due to its levo isomer. Atropine is widely used for resuscitation, anesthesia, ophthalmology, and as an antidote in organophosphate poisoning.

4. Mechanism of action Atropine is competitive antagonist of the acetylcholine at the M1, M2, M3, receptors. Antagonism is reversible. M1 and M3 receptors blockade occur by inhibition of release of IP3. M2 receptor mediated action causing inhibition of adenyl cyclase .

5. Natural sources Atropa belladonna (most common) Datura inoxia Datura stramonium Family: Solanaceae Part used: Dried leaves and flowering tops

6. Chemical constituents Atropa belladonna contains 0.3-1% total alkaloids including: Atropine Apoatropine Acetylcholine belladonnine

7. History Atropine extracts from Egyptian henbane were used by Cleopatra in the last century B.C. to dilate her pupils, in hope that she would appear more alluring. Atropine was first isolated in 1833 and first synthesized by German Chemist Richard Willstatter in 1901.

8. Extraction and isolation Atropine is tropane alkaloid and it can be extracted from plant by following way: 1. Drying and crushing to fine powder. 2. Extract it with ether to remove fats, waxes, oil, and waxes. 3. The material obtain is then extracted with alcohol and evaporated to leave crude alkaloid mixture. 4. The extract is then partitioned between diluted aqueous tartaric acid solution and ethyl acetate.

9. 5. Ethyl acetate layer contain neutral and weakly basic alkaloids which are obtained by evaporating this layer. 6. Aqueous layer is neutralized with ammonia and sodium carbonate and again extracted with ethyl acetate. The organic layer now contain basic alkaloids, while aqueous layer have quaternary ammonium ions.

10. Biosynthesis 1. The biosynthesis of atropine starts from L-phenylalanine which undergoes transamination lead to the formation of phenyl pyruvic acid.

11. 2. Phenyl pyruvic acid is then reduced to phenyl lactic-acid.

12. 3. Coenzyme A couples phenyl lactic acid with tropine to form littorine .

13. 4. Littorine undergo radical rearrangement initiated with P450 enzyme forming littorine aldehyde. 5. A dehydrogenase enzyme then reduces aldehyde to a primary alcohol making hyoscyamine , which upon racemization form atropine.