S_St_te_er_ro_oi_id_dS_S

Steroids comprise a group of

cyclical organic compounds whose

basis is a characteristic arrangement

of seventeen carbon atoms in a four-

ring structure linked together from

three 6-carbon rings followed by a 5-

carbon ring and an eight-carbon side

chain on carbon 17 (illustration on

right).

cyclical organic compounds whose basis is a characteristic arrangement of seventeen carbon atoms in a four- ring structure linked together from three 6-carbon rings followed by a 5- carbon ring and an eight-carbon side chain on carbon 17 (illustration on right).

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^TThese rⁱⁿings a^rre s^yyn^ththe^ss^iziz^eed by b^ioio^cc^hhem^icica^ll p^rro^ccess^ees^frfrom c^yy^cc^lil^ziza^tit^oion o^ff a

^thth^irir^tyty-ca^rrbon^cchaⁱⁿin^,, squa^lelene^,,ⁱⁿin^toto^lalanos^tete^rro^ll o^rr c^yyc^loloar^teteno^l.l.

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Hund^rreds o^ff d^isis^titⁿinc^tt s^tetero^idids a^rre^fofoundⁱⁿin an^imima^lsls^,,^fufung^i,i, p^lalan^tsts^,, and e^lslse where and many s^tete^rro^idids a^rre ne^cce^ss^ssa^rry^toto^lil^fi^efe a^tt a^lll^lele^vv^ee^lsls^..

^TTheyⁱⁿin^cc^lulude cho^leles^tetero^l,l,^ththe^ss^eex ho^rrmones es^trtrad^ioio^ll and^tete^ss^totos^teterone^,, b^ili^ele ac^idid^ss^,, and drugs such as^ththe an^tit^-i-ⁱⁿin^flf^alamma^totory agen^tt dexame^ththa^ssone^..

Steroids comprise a

group of

cLASSiFicAtioN

Various authors used slightly different means of classifying the steroids . But here the one selected here divides them into five categories depending on the type of substituent group at C-17,i.e., group R

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1^.S.S^tte^rr^oo^lsls^:-:- whe^rre R ^isis an a^lil^pipha^tit^cic s^dide chaⁱⁿin^.. ^TThey con^tataⁱⁿin usua^llyly one o^rr mo^rre^hh^yy^dd^roro^xx^yy^ll^gg^roro^uu^pp^ss a^ttata^cc^hh^eedⁱⁿin^aa^lil^cic^yy^cc^lil^cic^lilⁿin^kk^aa^gge

2^.S.Sex H^oo^rrm^oones^:-:- whe^rre R bea^rrs a ke^toton^icic o^rr h^yy^dd^rrox^yy^ll g^rroup and mos^lt^yly po^ss^ss^eess^aa^twtw^oo^cc^aa^rbrb^oon^ss^idid^ee^cch^aaⁱⁿin

3^.C.Car^dd^iaiac G^lylyc^oos^idide ^:-:- whe^rre R ^isis ^aa ^lala^cc^totoⁿn^ee ^rrⁱⁿin^gg ^.. The ^gg^lyly^cc^oo^ss^idides a^lslso ^cc^oon^tataⁱⁿins ^ssuga^rrs ^lilⁿin^kked ^thth^rrough ox^yygen ⁱⁿin o^ththe^rr pa^rr^tsts o^ff ^ththe mo^lelecu^lele^.. No^rrm^aa^llyly^ooⁿn^hh^yyd^rro^lyly^ss^isis^itit y^eie^ldlds^thth^isis^ssuga^rr ^totoge^ththe^rr w^itit^hh^cc^aa^rdrd^iaia^cc ag^lyly^cc^oon

4^.B.B^ili^ele Ac^idids^:-:- whe^rre R ^isis e^ss^ssen^tit^aia^llyly a^fif^viv^ee^--^cca^rrbon s^dide^cc^hhaⁱⁿin endⁱⁿing w^iti^hth a

^cc^aa^rrbox^yy^lil^cic a^cc^idid m^oo^ieie^tyty

5^.S.Sa^pp^oogenⁿin^ss^:-:- whe^rre R con^tataⁱⁿins an ox^aa^cc^yy^cc^lil^cic⁽(^ee^ththe^rr^aa^l)l)^rrⁱⁿin^gg^ss^yys^ete^mm^..

Sterols

The sterol may be further sub divided into the following three categories , namely:- (a)Zoosterols:- such sterols those are obtained from of plants are obtained from the animal kingdom only.

Example-

(i)Cholesterol, (ii)coprostanol.etc.

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(b)Phytosterols:-such sterols those are derived from the plant sources.

(c) Mycosterols :- such sterols those are obtained from either yeast or fungi.

Sex Hormones

Sex hormone are usually classified under the following three heads ,namely:-

1. Androgens(male hormones):-

2.Oestrogens(female hormones):-

(i)oestrone (ii)oestradiol (iii)stilbesterol (iv)hexesterol etc.

3.Gestogens(the carpus Luteum hormones):-

Example:-

Cardiac Glycosides

Example:-

digitoxine

DIGOXIN

Bile salt

The liver secretion a clear, golden yellow viscous liquid known as ‘bile’ .It is stored in gall bladder and is useful for digestive system.

Examples:-

Cholic acid

deoxycholic acid

Sapogenins

Sapogenins are the aglycones, or non-saccharide, portions of the family of natural products known as saponins. Sapogenins contain steroid or other triterpene frameworks as their key organic feature.

Examples:-

digitonin

diosgenin

Androgens & anabolic steroids

An_Andr_drog_ogens_ens &_& an_anaboli_abolic_c st_steroids_eroids

The term androgens includes a number of natural and synthetic compounds that exibite the masclinizing and anabolic action of testosterone.

The main physiological , endogenic , and androgenic hormonese. Androgen , commonly referred to as male sex hormones or anabolic steroids , in perticular ,testosteron ,are produced by male sex glands in the male body.

Test_tost_terone

It is the natural androgen secreted by the interstitial cells of the testis;

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it is necessary for normal spermatogenesis, for the development of the male secondary sex characteristics, and for the growth, at puberty, of the sexual apparatus.

I

^.A creamy white crystaline powder Melting point at 118-123 degree C ,

Insoluble in water,freely soluble in alcohol and in vegetable oil, It has short duration of action and half life about 4 hour.

Properties

Pathways of testosterone biosynthesis

Δ4-Androstendione

Testosterone

Me^chan

sm ^{of a}

tioⁿ

Testosteron bind to a specific receptor in a targe cell.testosteron itself is the active ligand in muscle an liver; but in others it must be metabolised to dihydrotestosterone (DHT) to show its action

Testosteron bind to a specific receptor in a target cell.testosteron itself is the active ligand in muscle an _d liver; but in others it must be metabolised to dihydrotestosterone (DHT) to show its action

Marketed products

Chemical names

• Testosterone Esters
• Nandrolone Esters
• Stanozolol
• Trenbolone Acetate
• Mesterolone
• Stanozolol

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Dose

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For prolonged treatment ,subcutaneously ,600 mg;

For brest cancer upto 1.5gm alternatively 10 to 30 mg per day through the buccal administration

side effects

•

Negative Effects

• Depression
• Violent behavior
• Bad breath
• Cancer causing
• Heart attack & Stroke
• Abdominal pain
• Possible infertility

USES:-

Treatment of breast cancer

Growth and development of male sex organs Important for (male) sex drive and performance Development of secondary sexual characteristics Important role in spermatogenesis

Testosterone is necessary for normal sperm development.

Fluoxymesterone

Fluoxymesterone is an anabolic steroid with strong androgenic properties that has been used in the treatment of male hypogonadism,

delayed puberty in males, and in the treatment of breast neoplasms in women.

It is approximately 5 times as potent as methyltestosterone.

The antitumor activity of fluoxymesterone appears related to reduction or competitive inhibition of prolactin receptors or estrogen receptors or production.

It is considered a very toxic oral drug.

the half-life of fluoxymesterone is about 9.2 hours.

Fluoxymesterone facilitates formation of body muscle mass and

strengthens the process of tissue development.

The main indications for using Fluoxymesterone , as well as

other anabolic steroids , are abnormal protein anabolism

asthenia ,diseases accompanied by protein loss, adrenal

insuficieny ,steroid diabetes ,and prolonged condition of

sluggishness

Fluoxymesterone facilitates formation of body muscle mass and strengthens the process of tissue development.

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The main indications for using Fluoxymesterone , as well as other anabolic steroids , are abnormal protein anabolism asthenia ,diseases accompanied by protein loss, adrenal insuficieny ,steroid diabetes ,and prolonged condition of sluggishness

SAR of Androgens

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1.For a substance to have activity ,it must contain the andostane skeleton.

2.Oxygen at C-3 and C-17 are not essential for the androgenic activity.

3. The basic nucleus having 5-beta-androstane which having androgenic activity

,whereas 5-alpha-androstane having no activity.

4. There should not be chain constriction or extension because it leads to finished the activity.
5. Introduction of 3-hydroxy group and 3-keto group enhance the activity. 6.Hydroxy group at C-17 position has no androgenic or anabolic activity. 7.Halogen substitution produces compounds with decreased activity except when

placed at C-4 or C-9 position. For example , 9-fluoro derivatives produces an anabolic effect 20 times that of 17 alpha-methyl testosterone

8.Halogen introduction will decrese the activity except the C-4 and C-9.

9.Introduction of double bond at C-1 position increases the anabolic activity for example – methandrostenolone is more active than methyltestosterone

10.Replacement of carbon atom at C-2 position by oygen (e.g. oxandrolone) gives the oral anabolic activity.

11.Removal of CH3 group in testosterone gives 19-nor testosterone with more anabolic activity and less androgenic activity when compared with testosterone.

12.The introduction of heterocyclic system into the steroid nucleus in ring A improve the anabolic activity . For example ,stanozolol are found to possess more anabolic activity, possessing pyrazole .

Estrogens

Estrogen are a group of steroid compounds that function as the primary female sex hormones.

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Three naturally occuring estrogen are estradiol,estriol and estrone ,In the body these are all produced from androgens through enzyme action.

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SOURCE:-

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Estrogen are produced by developing follicles in the ovaries , the corpus luteum and the placenta, some estrogens are also produced in smaller amounts by other tissues such as liver, adrenal glands and the breasts . These secondary source of estrogen are especially important in post menopausal women.

H:)

Dehydroeplandroste rone

3fi-OH-SDH

0

A ndroslenedlone

17-0H-SDH

16a-Hydroxyaodrostenedlone

ti7-0H-SDH,

.I,aromatase

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' H³C OH

,QH

17-0H-SDH

>- >

16r4-0Hase

16u-0Ha_.s_.e_.

I

3P-0-li-SD4

3 J-Hydro)(Vs.te rold

de hydro genase

7-0H-SD-1

17'-Hyd roxysterold

dehydro genase

16u-O A.S

16-a-Hydroxyla.se

The biosynthetic pathway for the estrogens

,..OH 3Jl-OH-S_.D_.H

HO

16a-Hydroxydehydro ­

eplandrost erone

aromala.5e

)Ill

HO

HO

aromatase

---->-

,..OH

Estradiol

Estradiol is a human sex hormone and steroid, and the primary female sex hormone. It is important in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is essential for the development and maintenance of female reproductive tissues ^,but it also has important effects in many other tissues including bone. While estrogen levels in men are lower compared to women, estrogens have essential functions in men as well.

Properties

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Creamy white crystalline powder , Hygroscopic in nature

Having melting point between173-179 degree; Insoluble in water and soluble in a alcohol

Conversion of testosterone to estradiol:-

Estradiol, like other steroids, is derived chain cleavage and using

from cholesterol. After side

the

key intermediary. A fraction of

turn

delta-5 or the delta-4

pathway,androstenedione is the

the androstenedione is converted to testosterone, which in

undergoes conversion to estradiol by an enzyme called aromatase.

Mechanism of action:-

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Estradiol acts primarily as an agonist of the estrogen receptor (ER), a nuclear steroid hormone receptor.

There are two subtypes of the ER, ERα and ERβ, and estradiol potently binds to and activates both of these receptors. The result of

ER activation is a modulation of gene transcription and expression in ER

expressing cells, which is the predominant mechanism by which estradiol mediates its biological effects in the body.

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DOSE:-

Oral,2mg per day; intramuscular ,1.5 mg 2 or 3 times weekly

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UESE:-

-- It helps to regulate and subsequent maintence of female sex organs, certain function of the uterus and all the secondary sex features and the mammary

glands.

Estriol

It is available for compounding into number of different formulation for use in Hormonal replacement therapy .

It can be used alone or its combination with estradiol or with estrone.

--Creamy white ,crystalline powder ,soluble in alcohol.

H:)

Dehydroeplandroste rone

3fi-OH-SDH

0

A ndroslenedlone

17-0H-SDH

16a-Hydroxyaodrostenedlone

ti7-0H-SDH,

.I,aromatase

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' H³C OH

,QH

17-0H-SDH

>- >

16r4-0Hase

16u-0Ha_.s_.e_.

I

3P-0-li-SD4

3 J-Hydro)(Vs.te rold

de hydro genase

7-0H-SD-1

17'-Hyd roxysterold

dehydro genase

16u-O A.S

16-a-Hydroxyla.se

The biosynthetic pathway for the estrogens

,..OH 3Jl-OH-S_.D_.H

HO

16a-Hydroxydehydro ­

eplandrost erone

aromala.5e

)Ill

HO

HO

aromatase

---->-

,..OH

Does:-

For menopausal symptoms, 250-500 mg per day.

Therapeutic use:-

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Estriol is used to mimic the activity of the naturally occurring female sex hormone oestrogen.

It is used in hormone replacement therapy (HRT).

it is used to treat problems associated with the vagina that are caused by a lack of oestrogen in the body.

It is used to relieve symptoms of menopause, or after surgery to remove the ovaries. this drug can include relief from symptoms associated with a lack of oestrogen including dryness and itching of the vagina, uncomfortable or painful sexual intercourse.

Treatment of symptoms associated with a lack of oestrogen To help wound healing after vaginal surgery

SAR of estrogen

1. Steroid nucleus is not necessary for estrogenic activity .Many constituents of plants like genstein ,coumestrol don’t contain steroid nucleus but possess estrogenic activity
2. The biologic activity varies with the mode of administration of estrogens . The order of activity of three naturally occuring steroids when administered subcutaneosly is estradiol ,estrone and estriol.the order of activity changes to estriol ,estradiol and estrone ,when the drugs are administered orally.
3. Estradiol is not effective orally due to rapid metabolism in liver but placement of ethinyl group at C-17 position increase the resistance to metabolic inactivation and make the compound orally effective .
4. Similarly methylation of 3-OH group .e.g. mesteranol make the compound orally effective
5. Easter derivatives (acetates and benzoates) of the naturally occuring and synthetic estrogens have prolonged action.
6. Insertion of OH group at C-6,C-7 and C-11 position reduces estrogenic activity.

Pr_ro_og_ge_es_st_ta_at_tio_on_na_al_l a_ag_ge_en_nt_t

They also called luteum hormoens ,mostly secreted by the corpus luteum portion of the ovary and the metabolised to various inactive products ,e.g. pregnanediol.

The metabolites are essentially excreated through urine.

PROGESTERONE

The natural progestational hormone is progesterone , which is secreated by the corpus luteum in the second part of the menstrual cycle.

Small amounts are also secreted by the testis in the male and the adrenal cortex in both sex and large amounts are secreted by the placenta.

PROGESTERONE

Synthesis:-

Acetylation of diosgenin at 200 degree C gives the corresponding diosgenyl diacetate which upon oxidation with chromium-6-oxide removes the side chain at C-17 and the resulting product on reduction followed by hydrolysis yields pregnelone .This on being subjected to Oppenauer oxidation affords the official compound.

DOSE:-

10-100 mg intra muscular

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uses

1. Prevent habitual abortion.
2. For treatment of functional uterine bleeding resulting due to the lack of oestrogens and progesterone
3. For treatment of dysmenorrhoea or painful menstruation 4.Pregnancy diagnosis,
5. Oral contraceptives,
6. For treatment of an advanced carcinoma of breasts. 7.To treat premature discomfort in the breasts 8.Progesterone can be used to treat catamenial epilepsy.

9.Progesterone also has a role in skin elasticity and bone strength, in respiration, in nerve tissue and in female sexuality, and the presence of progesterone receptors in certain muscle and fat tissue.

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Side effects:-

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The commonly asociated side-effects with progestin therapy are nausea, vomiting, drowsiness,edema ,irregular bleeding etc.

Adrenocorticosteroids

•Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

•Aldosteron

•Deoxycorticosterone etc.

Adrenocorticosteroids

are a class of chemicals that includes the steroid

hormones that are produced in the adrenal cortex of vertebrates, and synthetic analogues of these hormones. Corticosteroids are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

•Giucocorticoids such

as cortisol control carbohydrate, fat and protein

metabolism, and are anti-inflammatory by preventing phospholipid decreasing eosinophil action and a number of other mechanisms.

·Hydrocortisone(cortisol)

•Cortisone acetate etc.

release,

Glucocorticoids

Glucocorticoids may be categorized into three sub –groups as given-

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(a) Short-to medium acting glucocorticoids:-

Hydrocortisone

cortisone

prednisolone

(b) Intermediate acting glucocorticoids:-

(b) Long acting glucocorticoids:-

Triamcinolone

Flucortisone

Betamethasone

Dexamethasone

H_Hy_yd_dr_ro_oc_co_or_rt_ti_is_so_on_ne_e

^hhydrort^isis^ooⁿn^ee^isis a s^tete^rro^idid hormone^,, more spec^ifiⁱf^cic^aa^llyly a g^lulucoco^rr^tit^cico^idid^,, wh^icich^isis p^rroduced by ^ththe^zzona ^fafasc^icicu^lala^tata o^ff ^ththe ad^rrena^ll co^rr^tete^xx^..^ItIt ^isis ^rre^leleased ⁱⁿin respon^ss^ee^toto s^trtre^ss^ss and a ^lolow^lele^vve^ll o^ff b^lolood g^luluco^sse^..

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^ItI^sts ^fufunc^tit^oions are ^toto ⁱⁿin^cc^rrease b^lolood

^ssuga^rr^ththrough g^luluconeogenes^isis^,, ^toto supp^rress ^ththe^imimmune s^yys^tetem^,, and ^toto a^idid

^ththe me^tatabo^lil^sism o^ff ^fafa^t,t, pro^teteⁱⁿin^,, and ^cc^aa^rrbohydra^tete^..^ItIt a^lslso de^cc^rreases

^fofo^rrma^tit^oion^..

bone

P^rr^oo^pp^eert^ieies^:-:-

Wh^iti^ete c^rr^yy^ss^tata^llilⁿine powder

Havⁿing me^ltltⁿⁱing poⁱⁿin^tt 215 deg^rree

Ve^rry so^lulub^leleⁱⁿin wa^tete^rr so^lulub^leleⁱⁿin a^lclc^ooho^ll

Mechanism of action:-

D_Do_os_se_e:-_:-

Adu^ltlt^,o,o^rra^ll^fofo^rr rep^lalacemen^tt^,2,25^--50 mg^/d/day^,, ^fofor an^titiⁱⁿin^flf^alamma^toto^rry use^,, 20^--240 mg a day^..

• Cushing’s syndrome
• Osteoporosis
• Tendency to hyperglycaemia
• Negative nitrogen balance
• Increased appetite
• Increased susceptibility to infections
• Obesity, etc.

Adverse effects of Glucocorti- costeroids

Cushing’s syndrome

Contraindications

^•Peptic ulcer

^•Diabetes mellitus

^•Hypertension

^•Pregnancy (risk foetal defects)

^•Psychosis

^•Epilepsy

^•Chronic heart failure

^•Renal failure

Clinical uses:

• Allergic Rhinitis
• Rheumatoid Arthritis
• Asthma
• Multiple Sclerosis
• Carpal Tunnel Syndrome
• Gout
• Psoriasis
• Inflammatory Bowel Disease
• Sinusitis

Lupus Erythematosus

•

Prednisolone

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prednisolone is a glucocorticoid is four fold potent as but comparatively some what weaker as compare to hydrocortisone .

^ItIt essen^tit^aia^llyly has^ththe^fofo^llolowⁱⁿing chac^tete^rr^isis^tit^cic^ss^:-:-

• P^lala^ssma ha^lflf^lil^fif^ee^:-:- 3 hou^rr
• B^ioio^lolog^icica^ll ha^lflf^lil^fife^:-e :- 18^--36 hour^,,

^•Pha^rrmaco^kkⁱⁿine^tit^cics^:-:- dose dependen^tt because o^ff non^--^lilⁿinea^rr pro^teteⁱⁿin bondage

Prednisolone is prepared by the microbiological method starting with hydrocortisone using Corynebacterium simplex, which selectively cause dehydrogenation of the initial product at C-1 and C-2 position

Hydrocortisone

prednisolone

Incubation with

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Corynebacterium simplex

Do^sse^:-:- Adu^ltlt o^rra^l:l⁵:5^--60 mg per day; ^IMIM^/I/IV^inV in^jejec^tit^oion^:1:10^--40 mg^;; ^totop^icica^ll^:: 0^.2.25%

F_Fl_lu_ud_dr_ro_oc_co_or_rt_ti_ic_co_os_so_on_ne_e d_de_eo_ox_xy_yc_co_or_rt_ti_ic_co_os_st_te_er_ro_on_ne_e

Mine^rr^aa^ll^occ^o_o^rr^ttⁱi^cc^o_oⁱi^d s

A_Al_ld_do_os_st_te_er_ro_on_n

A_Al_ld_do_os_st_te_er_ro_on_n

Aldosterone is a steroid hormone (mineralocorticoid family) produced by the outer section (zona glomerulosa) of the adrenal cortex in the adrenal gland.

^•It plays a central role in the regulation of blood pressure,

^•increasing reabsorption of ions and water in the kidney,

^•aldosterone is pathogenic and contributes to the development and

progression of cardiovascular and renal disease,

•

Aldosterone has exactly the opposite function of the atrial natriuretic

hormone secreted by the heart.

^•It plays a central role in the regulation of blood pressure,

^•increasing reabsorption of ions and water in the kidney,

^•aldosterone is pathogenic and contributes to the development and progression of cardiovascular and renal disease,

^•Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.

t Sidt> chain cleavage enlyme

Preg n€! nol one I

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3 4lydroxyneroid dehydrogentJ5e

Progesterone I

t 2 I-hydroxylase

1 11-deoxyoort osterone I

11 hydroxylation

11 ·hydroxylation

T T -hydroxylase

I Cortlco ·terone I

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s..hydroxylation

rB..oxidation

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.Aidost@roIll@ I I Corticosterone

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LE!gCl'!n d:enzyme in blue,action performed in green .location in red.

[ 18-lrlydroxy-corticoste rone I

21-o-acetyl corticosterone

NOCl

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Nitrite derivatives

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Oxime

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CH3COOH NaNO2

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Semiacetal

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OH

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aldosterone

S_SA_AR_Ro_of_fA_Ad_dr_re_en_no_oc_co_or_rt_ti_ic_co_os_st_te_er_ro_oi_id_ds_s

1. All cortical steroids contains alpha, beta-unsaturated ketones in ring A and COCH2OH moiety attached to C-17 that has beta-configuration. These requirement are essential for mineralo corticoid activity

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• Oxygen at C-11 is essential for glucocorticoid activity.A hydroxy group is superior to C-11 keto group.

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• A 17 alpha-hydroxy increases glucorticoid activity.

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• Introduction of a fluoro to 6alpha or 9 alpha position increases both mineracorticoid and glucocorticoid activity.

6.Introduction of methyl or hydroxy at C-16 diminishes the minerao corticoid but has little effect on the antiinflammatory action.

5.Insertion of double bond at C-1, 2 position enhance the glucocorticoid and anti-inflammatory activity.