Related to Medicinal Chemistry

1. STEROIDS
Guided by- Presented by-
Dr. P. Ravisankar Arikati. Pooja
M. Pharm, PhD 16AB1R0006
Professor & HOD
Vignan Pharmacy College, Vadlamudi
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2. Contents:-
I. Introduction .
II. Systematic nomenclature of steroids.
III. Classification of steroids.
IV. Hormones.
a) Male sex hormones
b) Female sex hormones
V. Corticosteroids.
a) Glucocorticoids
b) Mineralocorticoids
VI. Uses of steroids.
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3. Introduction:-
• Steroid's is a biologically active organic compound with
four rings arranged in a specific molecular configuration.
• Steroid core structure is composed of 17C atoms bonded in
4 fused rings A,B,C - three 6 membered cyclohexane rings
and a 5 membered cyclopentane ring D combinedly called
“CYCLOPERHYDROPHENANTHRENE” ring.
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4. o Steroids when dehydrogenated with selenium at 360oC yield Diel's
hydrocarbon.
Steroids
o When the distillation with selenium at 420oC the steroids give
mainly chrysene and small amount of picene.
Steroids
Se, 360oC
Diel’s hydrocarbon
Se, 420oC
Chrysene Picene
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5. Systematic Nomenclature of Steroids:-
i. Steroids are the derivatives of cyclopentanoperhydro-
phenanthrene ring system. 4 rings are represented with letters
A,B,C,D. Rings A,B are fused either by cis/trans. The carbon
atoms of this ring system are numbered.
ii. The methyl grps at points of ring junction are called angular
methyl groups.
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6. ii. Grps that lie abv the plane if the molecule i.e. same side as
angular methyl grps are designated as (β)- substituents which
is represented by solid lines.
iii. Grps that lie below the plane of molecule i.e. trans to the
angular methyl grps are designated as (α)- substituents which
is represented by dotted lines.
iv. If the configuration of the substituent is unknown, its bond to
the nucleus is drawn as a wavy line & is indicated by (ε)
symbol.
v. In systematic nomenclature the nature of R grp at position 17
determines the base name of an individual steroid.
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7. Classification:-
Hormones
Steroids Non- Steroids
Sex hormones Adrenal cortical
hormones
Glucocorticoids
Mineralocorticoids
Male sex hormones
(Androgens)
Female sex
hormones
Estrogens
Progestin's
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8. Hormones:-
• A chemical substance produced in the body that ctrl &
regulate the activity of cells/organs.
• Serve as messengers, controlling & coordinating activities
throughout the body.
Sex hormones:-
• Group of steroids biosynthesized in the testis, ovaries,
adrenals & placenta of pregnancy.
• Regulate reproductive functions & sexual processes &
responsible for the development of secondary male & female
sex characteristics.
• These are 2 kinds:-
1. Male sex hormones
2. Female sex hormones
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9. Male sex hormones ( Androgens):-
• Hormones responsible for the ‘male’features & reproduction.
• Major androgen in males is ‘Testosterone’ produced by testes.
Women have very smaller amt of androgens too, produced by
ovaries.
• Dihydrotestosterone (DHT) & androstenedione are of equal imp
in male development.
• Androsterone & dehydroepiandrosterone (DHEA) are
metabolites of testosterone & DHT.
In 1931 Butenandt isolated the
1st male sex hormones namely
“Androsterone”.
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10. Testosterone:-
In 1935, testosterone was
isolated by E. Laqueru etal.,
• It is the primary male sex hormone & anabolic steroid.
• It is synthesized by Leydig’s cells in testes and smaller amt
by ovaries. FSH & LH of pituitary gland ctrl the secretions
of testosterone.
• It promotes secondary sexual characteristics like increased
muscle & bone mass, growth of body hair.
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11. Structure of Testosterone:-
• It is a steroid from androstane class containing a keto & hydroxyl grps
at 3 and 17 positions.
• Molecular formula of testosterone is C19H28O2.
• Biosynthesized in several steps from cholesterol & is converted in liver
to inactive metabolites.
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12. Medical Uses:-
• Treat symptoms of sexual dysfunction in men and hot flashes
in women.
• Treat certain forms of breast cancer.
• Hypogonadism ( Testosterone replacement therapy -TRT),
improved libido, increased bone mass, and increased sense of
well-being.
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13. Some other hormones include;
Androsterone Dehydroepiandrosterone
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14. Female sex hormones:-
• Female sex hormones/sex steroids play vital roles in sexual
development, reproduction, and general health.
• Sex hormone levels change over time; but most significant
changes happen during puberty, pregnancy, and menopause.
Types of female sex hormone:-
• In females, the ovaries and adrenal glands are the main
producers of sex hormones. Includes;
Estrogen
Progestin's
Small qty of
Testosterone
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15. Estrogens:-
• This is probably the most well-known “Female” sex hormone.
• Although the majority of estrogen production occurs in the ovaries, the
adrenal glands and fat cells produce small amounts of estrogen too.
• Estrogen plays a crucial role in reproductive and sexual development,
which begins when a person reaches puberty.
• It is synthesized in graffian follicle, corpus luteum, placenta from
cholesterol.
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16. Structure of Estrogen:-
Medical uses:-
• Inhibition of ovulation in combination with progestin's.
• Nutrition of an early embryo.
• Hormone replacement therapy for post menopausal women.
• Used in treatment of advanced, inoperable breast cancer &
prostate cancer.
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17. Classification of estrogens:-
1. Steroidal estrogens-
Estrone Estradiol
Estriol Ethinyl estradiol
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18. 2. Non- steroidal estrogens:-
Diethylstilbestrol
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19. Progestin's:-
Structural formula was worked out
by Adolf Butenandt (1933–1934).
Progestin is an endogenous steroid & involved in the menstrual cycle,
pregnancy & embryogenesis of humans & other species.
• Its levels increase during ovulation and spike during pregnancy.
• Small amt are also secreted by testes in male & adrenal cortex in both sexes.
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20. Classification of progestin's:-
1. Derivatives of progesterone –
Progesterone Hydroxyprogesterone-
caproate
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21. 2. Synthetic progesterone's –
Norethindrone Ethisterone
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22. Adrenal cortical hormones (Corticosteroids):--
Formation-
ADRENAL
GLANDS
Medulla
Catecholamine&a
mp;apos;s
(adrenaline)
Cortex
No. of steroid
hormones
(Corticosteroids)
ACTH
Synthesis
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23. Types of corticosteroids:-
Corticosteroids
Glucocorticoids
1. Cortisol
2. Corticosterone
Mineralocorticoids
1. Aldosterone
2. Deoxycorticosterone
1. Prednisolone
2. Dexamethasone
3. Betamethasone
Natural
Corticosteroids
Synthetic
Corticosteroids
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24. Glucocorticoids:-
• Glucocorticoids are endogenous compounds that have an
effect on carbohydrate, lipid, and protein metabolism.
• Immunodepressions and also possess anti-shock & anti-toxic
action.
Biological effects:-
1. Promote lipolysis due
to glucagon, growth-
hormone, adrenaline,
thyroxine.
2. Inhibit intestinal
absorption &
enhance renal excretion
of calcium.
3. Promote
glycogen
deposition in
liver.
4. Restrict
capillary
permeability.
5. Suppression
of inflammatory
response.
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25. Classification of Glucocorticoids:-
Natural E.g.- Cortisol ,Corticosterone
1.Cortisol:-
✓ It is known as hydrocortisone (stress hormone).
✓ It is synthesized from cholesterol.
Structure-
Medical uses:-
• Control blood sugar levels.
• Regulate metabolism.
• Reduce inflammation.
• Control blood pressure.
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26. 2. Corticosterone:- Also called 17- deoxy cortisol.
Positive effects:-
• Involved in regulation of energy.
• Immune reaction.
• Stress responses.
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27. Mineralocorticoids:-
• Mineralocorticoids are endogenous compounds that have an
effect on fluid and electrolytic balance in the body, mainly by
promoting sodium retention in the kidney.
Biological effects:-
1. Helps to maintain
body salt &
water levels
2. Regulates blood
pressure
3. Activate
reabsorptionof
sodium & Cl in
kidney canaliculi
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28. Classification of Mineralocorticoids:-
Natural e.g.- Aldosterone, Deoxycorticosterone
1. Aldosterone:- Main mineralocorticoid hormones.
• First isolated in crystalline form by Mason etal. in 1953.
Structure:-
Positive effects:-
• 4 times more than hydrocortisone.
• Promote Na+ and water retention, and lower plasma
K+ concentrations.
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29. 2. Deoxycorticosterone:-
• Also called 11-Deoxycorticosterone (DOC).
• Acts as a precursor to aldosterone.
Structure:-
Medical use:-
• Used to treat adrenal insufficiency.
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30. Synthetic corticosteroids:-
1. Prednisolone:- Modified derivative of cortisone.
Structure:-
Medical uses:- Arthritis, immune system disorders, breathing
problems, cancer & severe allergies.
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31. 2. Dexamethasone:-
• It is 16 α- methyl derivative of prednisolone.
• Shows higher glucocorticoid & anti- inflammatory activity but
mineralocorticoid activity is low.
Structure:-
Medical uses:-
Rheumatic problems, skin diseases, severe allergy, chronic
obstructive lung disease etc.,
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32. 3. Betamethasone:-
• It has same structure as dexamethasone but methyl grp at 16 position is
in β- configuration.
Structure:-
Medical uses:- treat a variety of skin conditions (e.g., eczema, dermatitis,
allergies, rash) & reduces the swelling, itching & redness.
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33. Uses of Steroids:-
• Used to increase muscle mass & decrease fat.
• Adrenocortical Insufficiency.
• Allergic reactions.
• Chronic obstructive pulmonary disease (COPD).
• Connective tissue disorders.
Contraindications & Side effects of Steroids:-
• Skin discoloration.
• Acne & blurred vision.
• Osteoporosis.
• Diabetes mellitus.
• Risk foetal defects.
• Psychosis.
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34. References:-
1) Principles of medicinal chemistry – Ramarao Nadendla.
2) Wilson & Giswolds TB of medicinal chemistry
3) Foye principle of medicinal chemistry.
4) Article journals.
5) Textbook of medicinal chemistry – V. Alagarsamy.
6) Google browsing.
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