STEROIDS

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'sisabiologicallyactiveorganiccompoundwith
fourringsarrangedinaspecificmolecularconfiguration.
•Steroidcorestructureiscomposedof17Catomsbondedin
4fusedringsA,B,C-three6memberedcyclohexanerings
anda5memberedcyclopentaneringDcombinedlycalled
“CYCLOPERHYDROPHENANTHRENE” ring.
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4. oSteroidswhendehydrogenatedwithseleniumat360
o
CyieldDiel's
hydrocarbon.
Steroids
oWhenthedistillationwithseleniumat420
o
Cthesteroidsgive
mainlychryseneandsmallamountofpicene.
Steroids
Se,360
o
C
Diel’s hydrocarbon
Se,420
o
C
Chrysene Picene
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5. Systematic Nomenclature of Steroids:-
i.Steroidsarethederivativesofcyclopentanoperhydro-
phenanthreneringsystem.4ringsarerepresentedwithletters
A,B,C,D.RingsA,Barefusedeitherbycis/trans.Thecarbon
atomsofthisringsystemarenumbered.
ii.Themethylgrpsatpointsofringjunctionarecalledangular
methylgroups.
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6. ii.Grpsthatlieabvtheplaneifthemoleculei.e.samesideas
angularmethylgrpsaredesignatedas(β)-substituentswhich
isrepresentedbysolidlines.
iii.Grpsthatliebelowtheplaneofmoleculei.e.transtothe
angularmethylgrpsaredesignatedas(α)-substituentswhich
isrepresentedbydottedlines.
iv.Iftheconfigurationofthesubstituentisunknown,itsbondto
thenucleusisdrawnasawavyline&isindicatedby(ε)
symbol.
v.InsystematicnomenclaturethenatureofRgrpatposition17
determinesthebasenameofanindividualsteroid.
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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:-
•Achemicalsubstanceproducedinthebodythatctrl&
regulatetheactivityofcells/organs.
•Serveasmessengers,controlling&coordinatingactivities
throughoutthebody.
Sexhormones:-
•Groupofsteroidsbiosynthesizedinthetestis,ovaries,
adrenals&placentaofpregnancy.
•Regulatereproductivefunctions&sexualprocesses&
responsibleforthedevelopmentofsecondarymale&female
sexcharacteristics.
•Theseare2kinds:-
1.Malesexhormones
2.Femalesexhormones
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9. Male sex hormones ( Androgens):-
•Hormonesresponsibleforthe‘male’features&reproduction.
•Majorandrogeninmalesis‘Testosterone’producedbytestes.
Womenhaveverysmalleramtofandrogenstoo,producedby
ovaries.
•Dihydrotestosterone(DHT)&androstenedioneareofequalimp
inmaledevelopment.
•Androsterone&dehydroepiandrosterone(DHEA)are
metabolitesoftestosterone&DHT.
In 1931 Butenandt isolated the
1
st
male sex hormones namely
“Androsterone”.
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10. Testosterone:-
In 1935, testosterone was
isolated by E. Laqueru etal.,
•Itistheprimarymalesexhormone&anabolicsteroid.
•ItissynthesizedbyLeydig’scellsintestesandsmalleramt
byovaries.FSH&LHofpituitaryglandctrlthesecretions
oftestosterone.
•Itpromotessecondarysexualcharacteristicslikeincreased
muscle&bonemass,growthofbodyhair.
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11. Structure of Testosterone:-
•Itisasteroidfromandrostaneclasscontainingaketo&hydroxylgrps
at3and17positions.
•MolecularformulaoftestosteroneisC19H28O2.
•Biosynthesizedinseveralstepsfromcholesterol&isconvertedinliver
toinactivemetabolites.
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12. MedicalUses:-
•Treatsymptomsofsexualdysfunctioninmenandhotflashes
inwomen.
•Treatcertainformsofbreastcancer.
•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:-
•Femalesexhormones/sexsteroidsplayvitalrolesinsexual
development,reproduction,andgeneralhealth.
•Sexhormonelevelschangeovertime;butmostsignificant
changeshappenduringpuberty,pregnancy,andmenopause.
Types of female sex hormone:-
•Infemales,theovariesandadrenalglandsarethemain
producersofsexhormones.Includes;
Estrogen
Progestin's
Small qty of
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15. Estrogens:-
•Thisisprobablythemostwell-known“Female”sexhormone.
•Althoughthemajorityofestrogenproductionoccursintheovaries,the
adrenalglandsandfatcellsproducesmallamountsofestrogentoo.
•Estrogenplaysacrucialroleinreproductiveandsexualdevelopment,
whichbeginswhenapersonreachespuberty.
•Itissynthesizedingraffianfollicle,corpusluteum,placentafrom
cholesterol.
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16. Structure of Estrogen:-
Medical uses:-
•Inhibitionofovulationincombinationwithprogestin's.
•Nutritionofanearlyembryo.
•Hormonereplacementtherapyforpostmenopausalwomen.
•Usedintreatmentofadvanced,inoperablebreastcancer&
prostatecancer.
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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).
Progestinisanendogenoussteroid&involvedinthemenstrualcycle,
pregnancy&embryogenesisofhumans&otherspecies.
•Itslevelsincreaseduringovulationandspikeduringpregnancy.
•Smallamtarealsosecretedbytestesinmale&adrenalcortexinbothsexes.
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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:-
•Glucocorticoidsareendogenouscompoundsthathavean
effectoncarbohydrate,lipid,andproteinmetabolism.
•Immunodepressionsandalsopossessanti-shock&anti-toxic
action.
Biologicaleffects:-
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:-
NaturalE.g.-Cortisol,Corticosterone
1.Cortisol:-
✓Itisknownashydrocortisone(stresshormone).
✓Itissynthesizedfromcholesterol.
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:-
•Mineralocorticoidsareendogenouscompoundsthathavean
effectonfluidandelectrolyticbalanceinthebody,mainlyby
promotingsodiumretentioninthekidney.
Biologicaleffects:-
1. Helps to maintain
body salt &
water levels
2. Regulates blood
pressure
3. Activate
reabsorption of
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:-
Medicaluses:-Arthritis,immunesystemdisorders,breathing
problems,cancer&severeallergies.
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31. 2. Dexamethasone:-
•Itis16α-methylderivativeofprednisolone.
•Showshigherglucocorticoid&anti-inflammatoryactivitybut
mineralocorticoidactivityislow.
Structure:-
Medicaluses:-
Rheumaticproblems,skindiseases,severeallergy,chronic
obstructivelungdiseaseetc.,
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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 ofskinconditions (e.g.,eczema,dermatitis,
allergies, rash) & reduces the swelling,itching & redness.
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33. Uses of Steroids:-
•Usedtoincreasemusclemass&decreasefat.
•AdrenocorticalInsufficiency.
•Allergicreactions.
•Chronicobstructivepulmonarydisease(COPD).
•Connectivetissuedisorders.
Contraindications&SideeffectsofSteroids:-
•Skindiscoloration.
•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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