Steroidal Drugs

By

Dr. N.C. Baruah

Chemistry of Steroids

• Steroids are tetra cyclic compounds.

• Steroids are derivatives of Cyclopentanoperhydrophenanthrene.

• The phenanthrene and the cyclopentane ring is fused in steroids,

• The ring system is completely saturated (hydrogenated) and is referred to as a cyclopentanoperhydrophenanthrene.

• Steroids on dehydrogenation with selenium at 360°C gives Diel’s hydrocarbon

• (17-methylcyclopentanoperhydrophenanthrenes)

Classification of steroids

• The steroids are classified as Estrane, Androstane, Pregnane and Cholestane.

• All other steroids are the derivatives of these classes.

Estrane (C18) Androstane (C19)

Classification

• Pregnane (C21) Cholestane (C27)

Nomenclature of steroids

• The numbering of the carbon atoms in steroids remain

fixed.

• If a carbon is absent in its position the rest of the

numbering remain unchanged. ‘Nor’ is used to indicate

absence of methylene gr. or terminal methyl group.

• A solid line denotes a group above the plane is β-

configuration, dotted line denotes below the plane (α-

configuration)

Nomenclature of steroids

• If there is any double bond in the steroid structure,

– The suffix ‘-ane’ of the parent name

– is replaced with

– ‘-ene’ if one double bond is present,

– ‘-diene’ if two double bonds are present,

– ‘-triene’ if three double bonds are present, and so forth.

Major classes of natural steroids • Hormones produced by gonads:

• Testosterone (androgenic & anabolic)(C 19)

• Estrogens(C 18)

• Progestogens (C 21)

• Hormones produced by adrenal gland:-

• Cortisol (glucocorticoids),

• Aldosterone (mineralocorticoids),

• Bile acids and salts of Cholic acids,

• Sterols – Cholesterol, Ergosterol, Stigmasterol.

Hormones produced by gonads

Estradiol Estrone

• Testosterone Progesterone

Hormones produced by adrenal gland

• Cortisol

• Aldosterone

Bile acids and salts-bile acids

• Cholic acid

Deoxycholic acid

• Chenodeoxycholic acid

Cholesterol

.

Biosynthesis of steroids

• Estrogens are biosynthesized from cholesterol in the ovary.

• During pregnancy, the placenta begins to synthesize estrogen.

• Progesterone is biosynthesized in corpus luteum.

• Estrogens and progesterone are the two most important female sex hormones.

Biosynthesis of steroids

• Testosterone (male sex hormones) is synthesized from cholesterol in the testes.

• These hormones are also synthesized in little amounts in extra glandular sites, particularly in adipose tissues.

. Cholesterol

Pregnenolone

17-Hydroxypregnenolone Progesterone Dehydroepiendrosterone

Androstenedione

Estrone Testosterone

Estradiol

Role of Gonadal hormones

• The Gonadal hormones play important roles in

reproduction, in the menstrual cycle, and in giving women and men their characteristic physical differences.

• The estrogen and its derivatives have the estrogenic activity in maintaining homeostasis, cell division and protein expression.

• The synthetic or semisynthetic progesterone derivatives are commonly called progestins.

• The major functions of progesterone is preparation of the uterus for pregnancy, maintenance of pregnancy and in maintenance of the female reproductive organs.

• The estrogens and progestins are most extensively used as chemical contraceptive agents for women and in hormone replacement therapy (HRT).

Role of Gonadal hormones

• Testosterone has androgenic (promoting male physical characteristics) and anabolic (muscle building) activities.

• Many synthetic androgenic and anabolic steroids have been prepared and are used to recover from debilitating illness.

• All anabolic steroids have androgenic effects.

Role of Gonadal hormones

• Estrogen products: Estradiol, Estrone, Estriol, Ethinylestradiol.

• Progestins: Progesterone, Hydroxyprogesterone, Medroxyprogesterone, Megestrol, Nomegestrol, Norethindrone, Norgestrel etc.

• The female sex hormones are widely used for the treatment of various gynecological diseases such as primary or secondary amenorrhea, dysmenorrhea and endometriosis.

• The estrogen and progestins are used as Oral Contraceptives.

Role of Gonadal hormones

• The anabolic steroids enhance Skeletal mineralization and bone maturation. They have marked nitrogen retention activity.

• The anabolic agents decrease calcium excretion by the kidney and result in increased deposition of both calcium and phosphorous in bone.

• They also increase red blood cell formation.

The adrenocortical hormones

• The glucocorticoids and mineralocorticoids are secreted by the adrenal gland under the influence of peptide hormones secreted by the hypothalamus and anterior pituitary lobe (adenohypophysis).

• The anterior pituitary hormone that influences glucocorticoids synthesis is adrenocorticotropic hormone (ACTH; corticotrophin).

• The corticotrophin-releasing factor (CRF) is released by the hypothalamus that stimulate the anterior pituitary to release of ACTH into the bloodstream.

The adrenocortical hormones

• ACTH stimulates the synthesis and secretion of the glucocorticoids.

• The synthesis and secretion of glucocorticoids is regulated in a negative feedback mechanism by adrenal-anterior pituitary-hypothalamus axis.

• Aldosterone secretion rates are influenced to a greater extent by the octapeptide angiotensin-II.

. Cholesterol

Progesterone 17-Hydroxyprogesterone

Desoxycorticosterone 11-Desoxycortisol

Corticosterone Cortisol

Aldosterone

Glucocorticoids

• Glucocorticoids are used as powerful anti-inflammatory and antiallergic agents.

• The Mineralocorticoids (MC) are used for the treatment of Addison disease.

• Addison disease is caused by chronic adrenocortical insufficiency, which may be due to either adrenal or anterior pituitary failure.