Adrenocorticoids and chemistry of Vitamin- D.pptx

It contains information about adrenocorticoids and chemistry of vitamin D

1. PRESENTED BY PABBA SUPRAJA 1008-21-884-018 M.PHARM 1 ST SEMESTER PHARMACEUTICAL CHEMISTRY UNIVERSITY COLLEGE OF TECHNOLOGY OSMANIA UNIVERSITY UNDER THE GUIDANCE OF DR. S. ANITHA FACULTY OF PHARMACY UCT, OSMANIA UNIVERSITY ADRENOCORTICOIDS AND CHEMISTRY OF VITAMIN- D

2. ADRENOCORTICOIDS •These are the hormones released from adrenal glands. The adrenal glands are flattened, cap-like structures located above the kidneys. The inner core (medulla) of the gland secretes Catecholamines , whereas the shell (cortex) of the gland synthesizes steroid hormones known as Adrenocorticoids or Adrenocorticosteroids. • The term adrenocorticosteroids ( a-dree-noe-KOR-ti-KO-ster-oids ) refers to a group of agents secreted by the adrenal cortex. • Also called as Adrenal corticosteroids or Corticosteroids. •Adrenal cortex consists of three parts : 1. Zona reticulosa 2. Zona fasiculata 3. Zona glomerulosa

3. • Zona fasiculata :- Glucocorticoids Zona glomerulosa :- mineralocorticoids. *CLASSIFICATION : The adrenal cortex Synthesizes two classes of steroids. they are as follows: Glucocorticoids: The word glucocorticoid was derived from “glucose + cortex + steroid” to reflect their : a) role in regulating glucose metabolism b) adrenal cortex origin c) steroidal structure -Endogenous glucocorticoids are part of the feedback mechanism the body utilizes to reduce immune activity (inflammation) .

4. -Exogenous glucocorticoids are used to treat diseases caused by an overactive immune system (eg. allergies, asthma, autoimmune diseases and sepsis. -Glucocorticoids are distinguished from mineralocorticoids and sex hormones that have different receptors, target cells and effects. Mineralocorticoids: A class of steroid hormones that cause retention of sodium and water. Aldosterone is the most importment endogenous mineralocorticoid. -Aldosterone’s physiological role is essential in maintenance of adequate fluid volume needed for normal cardiac output and blood pressure. -Without adequate levels of mineralocorticoids, diminished cardiac output can result in fatal shock.

5. Based on duration of action , Glucocorticoids are further classified as : 1. Short acting :- - t1/2 is less than 12 hours Eg: Hydrocortisone, cortisone. 2. Intermediate acting :- - t1/2 is betweenj 12-36 hours Eg : Predisolone Methyl predisolone Triamcinolone 3. Long acting :- -t1/2 is greter than 36 hours Eg : Dexamethazone Betamethasone Glucocorticoids Short acting Intermediate acting Long acting

6. *STRUCTURE AND NOMENCLATURE: － same as sex hormones. All are steroids, consequently the rules that define their structures, chemistry, and nomenclature are the same. － Adrenocorticoids consists of four fused rings ( A,B,C and D). － Chemically these hydrocarbons are “ cyclopentano perhydro phenanthrenes” . － D ring- five-memebered cyclopentane A,B,C rings- phenanthrene rings ( saturated derivative) － The polycyclic hydrocarbon, known as 5 alpha- cholestane , is used to illustrate the numbering system.

7. － Solid lines denote the groups above the plane of the nucleus (β- configuaration) and dotted or broken lines denote groups below the plane ( ɑ- configuaration). － If the configuaration of substituent is unknown, its bond to the nucleus is drawn as a wavy line. － The configuaration of the H at C-5 is always indicated in the name. － When a methyl group is missing from the side chain, this is indicated by the prefix ‘nor’ with the number of carbon atom, which has disaapeared. － The symbol Δ is often used to designate a C=C bond in a steroid. If C=C is in between carbons 5and 4 the compound is referred to as a Δ 4 steroid .

8. Structures of Adrenocorticoids :

9. SYNTHESIS OF ADRENOCORTICOIDS FROM CHOLESTEROL :

10. * CORTISONE : - a C21-steroid that is pregn-4-ene substituted by hydroxy groups at positions 17 and 21 and oxo group at positions 3, 11 and 20. -IUPAC NAME : 17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,11-dione. -Molecular formula : C 21 H 28 O 5

11. - White crystalline powder. - Insoluble in water and soluble in alcohol. - Naturally-occurring corticosteroid metabolite. - Also used as a pharmaceutical prodrug. -Cortisone is the inactive precursor molecule of the active hormone cortisol , which is the hydroxylation product of cortisone by 11-beta-steroid dehydrogenase. -It derives from a hydride of a pregnane.

12. MECHANISM OF ACTION OF CORTISONE :

13. -used to treat a variety of cancers, such as leukemia, lymphoma, and multiple myeloma. •used to treat nausea and vomiting associated with some chemotherapy drugs. -Cortisone is used to stimulate appetite in cancer patients with severe appetite problems. •The lotion (topical) is used in treatment of allergic skin reactions, and relieves symptoms of itching, redness, and swelling. -Cortisone is also used to replace steroids in conditions of adrenal insufficiency (low production of needed steroids produced by the adrenal glands). USES OF CORTISONE • used as an anti-inflammatory medication. -used to treat or prevent allergic reactions. •used as treatment of certain kinds of autoimmune diseases, skin conditions, asthma and other lung conditions.

14. CHEMISTRY OF VITAMIN - D •Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. • Upto now five vitamins of this group have been isolated, viz. D 1 , D 2 , D 3 , D 4 , and D 5 . • Vitamin D 1 or D is the molecular compound of D 1 and lumisterol. • Biologically vitamin D is termed as Calciferol. • It is also known as “ Sunshine Vitamin” , because the sterols which are present in the skin can be converted to vitamin D with the help of UV rays from the sun.

15. • Acts as hormone because it is synthesized in the body. • All the vitamins of this group are formed by irradiation of the specific sterols. These sterols are known as “Pro- Vitamins” . VITAMINS PRO- VITAMINS Vitamin D 2 (Ergocalciferol) Ergosterol Vitamin D 3 ( Cholecalciferol ) 7-dehydro-cholesterol Vitamin D 4 22,23-dihydroergosterol Vitamin D 5 7-dehydro-sitosterol

16. DISCOVERY OF VITAMIN- D → In the early 19th centuary, Edward Mellanby noticed dogs that were fed cod liver oil did not develop rickets and concluded vitamin A, or a closely associated factor, could prevent the disease. → In 1914 Elmer McCollum and Marguerite Davis discovered a substance in cod liver oil which later was called "vitamin A". → Later in 1922 McCollum tested modified cod liver oil in which the vitamin A had been destroyed. The modified oil cured the sick dogs, so he concluded the factor in cod liver oil differs from vitamin A. He called it vitamin D because it was the fourth vitamin to be named. → In 1932 Askew et al . isolated vitamin D 2 from irradiation mixture of ergosterol. windaus and Linsert proved vitamin D 1 as the adduct between vitamin D 2 and lumisterol.

17. CHEMISTRY :  Vitmin D is a generic term and consists of similar structure as steroids.  The A, B,C and D ring structure is derived from cyclopetanoperhydrophenanthrene ring structure of steroids. A B C  The only difference between steroids and vitamin D is that one of the rings in vitamin D are broken. In vitamin D the 9,10 carbon- carbon bond of ring B is broke so it is indicated as “9, 10- seco” in the nomanclature.  The numbering will be same as the parent compound cholesterol. A B C D

18. The IUPAC name of vitamin D 2 is 9,10- secoergosta- 5,7,10 (19), 22- tetra-en-3-ol. and the IUPAC name of vitamin D 3 is 9,10- seco-cholesta- 5,7,10(19)- trien-3-ol.

19. All the pro- vitamins of vitamin D possess certain essential characteristics : -OH group at C 3 position -Two conjugated double- bonds between C 5 - C 6 and C 7 - C 8 -A Hydrocarbon chain at C 17 . Vitamin D 1 contains molecular compound of lumisterol and vitamin D 2 in 1:1 ratio.

20.  Transformation of inactive pro-vitamins into active vitamins is accomplished by ultraviolet rays .

21.  V itamin D 2 and vitamin D 3 are not stable forms so they are converted into biologically active and stable form, Calcitriol in kidneys. It occurs in 2 steps 1. coverts to calcidiol in liver 2. converts to calcitriol in kidneys. calcifediol

22. DIETARY SOURCES :  Sunlight is the major source.  Found mainly in the cod- liver oil and other fish liver oils.  Egg yolk is another rich source of vtamin D.  Ergocalciferol occurs naturally in some mushrooms. Cholecalciferol occurs naturally in some fish like eel, tuna, salmon, catfish.  Milk and plant foods are poor sources of vitamin D.

23. MECHANISM OF ACTION OF VITAMIN - D

24. FUNCTIONS OF VITAMIN- D VITAMIN D FUNCTIONS CLASSICAL ACTIONS NON- CLASSICAL ACTIONS Calcium and phosphate homeostasis Bone mineralisation Regulation of cell proliferation and differentation Regulation of immune function Endocrine effects Insulin resistance Inflammation Modulation of Renin angiotensin system Renal function Muscle function

25. VITAMIN D DEFICIENCY • Rickets is the primary disease caused by vitamin D deficiency in young and children. • Osteomalacia - occurs in adults • Milk fever is seen in cattle • Osteoporosis • In polutry leads to reduced egg production • Infectious diseases • Inflammatory bowel disease :Crohn's disease and ulcerative colitis • Other conditions include diabetes, depression, schizoprenia, weight loss ,dementia.

26. REFERENCES : 1.WILSON and GISVOLD’S text book of organic medicinal and pharmaceutical chemistry, twelfth edition John M. Beale, Jr. John H. Block. 2. An introduction to Medicinal chemistry by GRAHAM L. PATRICK. 3. Thomas L. Lemke; David A. Williams (2008). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 889–. ISBN 978-0-7817-6879-5. 4. ChemIDplus Chemical Information Classification. 5.Norman AW (August 2008). "From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health". The American Journal of Clinical Nutrition.