Steroids

This slide gives you complete description about SAR and MOA with structures.

1. STEROIDS By SHAIKH SANIYA

2. Steroids has a wide distribution in nature and are formed by similar biochemical pathways. Steroids have broad functions in physiology, they act as Male sex hormone .Eg: testosterone. Female sex hormone. Eg: estradiol, progesterone. Anti inflammatory agent Eg: cortisone. Cardiac steroids Eg: digitoxigenin. Diuretics Eg: spironolactone. Digestants .Eg:dihydrocholic

3. Steroids consists of 4 fussed rings designated as A,B,C and D. The 4 ring structure is cyclo pentanoperhydrophenanthrene. It consist of cylopantane ring D and 3 ring structure of perhydrophenanthrene Basic Skeleton

4. Steroids are named as derivatives of Gonane (C17) Estrane (C18)

5. Androstane (C19) Pregnane (C21)

6. Cholestane (C27)

7. The target cell contain receptor in cytoplasm which react with steroid. The steroid receptor complex enter the cell nucleus by translocation. The complex binds with chromatin and this triggers the synthesis of mRNA. The mRNA moves out into cytoplasm and acts as a template for protein synthesis. Mode of action of steroid hormone

8. 1 ) Adrenocorticoid Classification of steriods Mineralocorticoids Eg: Aldesterone ,deoxycorticosterone, Fludrocortisone. b ) Glucocorticoids Eg: cortisone , hydrocortisone, corticosterone, prednisone , prednisolone

9. 2) Sex hormones Estrogens Eg : estrone , erstradiol , estratriol b) Progestin Eg:progesterone and derivatives, testosterones c) Androgens Eg: testosterone

10. a) Mineralocorticoids They affect mainly the metabolism of electrolytes and water. Eg: aldesterone ,deoxycorticosterone. They cause retention of Na+, PO4, Ca ,HNO3 and reduction of serum K+ Mineralocorticoids are useful in treatment of Addison’s disease. Deoxycorticosterone and fludrocortisone are used as replacement for aldosterone . 1.Andrenocorticoids ( secreated by adrenal gland)

11. 1.Aldosterone 2.Deoxycorticosterone EXAMPLES

12. 3.Fludrocortisone

13. Mainly affect carbohydrates, protein metabolism and lipid metabolism. Eg: cortisone, Hydrocortisone, corticosterone. They causes deposition of glycogen. They promote gluconogenesis, i.e formation of carbohydrate from non-carbohydrate molecule. The affect muscle tone, gastric secretion etc. b) Glucocorticoids

14. Cortisone Hydrocortisone

15. Prednisone Methyl prednisone

16. All the Adrenocorticoid have parent structure of pregnane C21, all trans backbone is essential for activity. Replacement of OH group at C21 with F increases activity, while replacement with Cl or Br decreases activity. The 11 beta OH group is involved in drug receptor binding, cortisone may be reduced to hydrocortisone as the active agent. The 9 alpha- flouro group increase glucocorticoid activity. SAR of Adrenocorticoid

17. Substituent's which increase both glucocorticoid and mineralocorticoid activity. 16 alpha methyl group and 16 beta methyl group decreases mineralocorticoid activity.

18. a)Estrogen It brings about the development of secondary sexual characteristics in females such as growth of hairs, growth of breast mainly produced by ovary, placenta, adrenal cortex. Eg : Estrone 2) Sex hormones

19. Estradiol Estratriol

20. Estrogen does not require a strict steroidal structure for activity hence compound with non steroidal nucleus can also posses estrogenic activity. DES can be viewed as a form of estradial with ring B & C open & 6C and D ring. i.e. SAR of estrogens

21. Reduction of double bonds of DES results in two diasteromers of hexesterol. USES OF ESTROGENS Prevention and treatment of post menopausal osteoporosis and other deficiency diseases. In abnormal uterine bleeding. In failure of ovarian development. As oral contraceptive with progestins .

22. b. Progestogens After ovulation takes place, corpus luteum is formed. It produces the hormone progesterone which maintains pregnancy and prevents ovulation during pregnancy. Progestin are compound that have biologic activities similar to progesterone. They include 2 structural classes a)progesterone and derivatives b)testosterones

23. Progesterone Medroxy Progesterone

24. Megesterol Norgestrel

25. Steroidal nucleus is important for progestational activity. The synthetic progestin's are of different types: a. prognane derivatives b. androthane derivatives c. estrane derivatives Ethisterone has a progestational as well as androgenic activity. Removal of 19 CH3 group decreases androgenic activity. SAR of Progestins

26. In male , FHS &LH are released under the regulation of hypothalamus. FSH promotes sperm development or spermatogenesis & LH stimulates the interstitial leying cells to secrete androgens. The important androgen is testosterone. Testosterone c) Androgens

27. Testosterone has 2 main activities Androgenic or male sex characteristic promoting activity. Anabolic or muscle building activity. It increase rate of protein synthesis & decrease rate of protein breakdown.

28. 17 Alpha methyl testosterone Oxymesterone

29. Androgens are regarded as derivatives of aldosteron. Steroidal nucleus is essential for the androgenic activity. Introduction of 3 keto & 17 alpha group increases androgenic activity. Increase in the length of alkyl side chain at C17 alpha decrease activity. Esterification of testosterone at C17 with no. of acids results in a long DOA SAR Of Androgens

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