Mineralocorticoids, Synthesis, Structure-Activity Relationship, Mechanism Of Action.

1. Prepared By-
Biplajit Das
Roll No- 06
B.Pharm 4th Year(7th Semester)
Department Of Pharmaceutical Sciences
Dibrugarh University, Dibrugarh, Assam,786004

2. CONTENTS
 Introduction
 Types of Corticosteroids
 Different Drugs With Their Chemical Structures
 Mineralocorticoids
 Synthesis of Mineralocorticoid
 Mechanism of Action
 Structure Activity Relationship
 Functions
 Marketed Drugs
 References

3. Introduction
 The adrenal cortex secretes steroidal hormones which
have glucocorticoid, mineralocorticoid and weakly
androgenic activities. Conventionally a term ‘corticoid’
and ‘corticosteroid’ includes natural gluco- and
mineralo-corticoids and their synthetic analouges.

4. Types of Corticosteroids
*Natural Corticosteroids
 Glucocorticoids- Cortisol, Corticosterone
 Mineralocorticoids- Aldosterone, Deoxycorticosterone
*Synthetic Corticosteroids
 Prednisolone
 Betamethasone
 Dexamethasone

5. Different Drugs with their Chemical Structure
Cortisol Corticosterone Aldosterone
Prednisolone Betamethasone Dexamethasone

6. Mineralocorticoids
 Mineralocorticoids (mineral+cortex+steriod) are the
class of steroidal hormones that composed of 21
carbon atoms and secreted by the zona glomerulosa
which is present on the outer zone of adrenal cortex
and regulate the fluid and electrolyte balance in the
body.
 Mineralocorticoids play a major role in regulating the
balance of electrolyte and water, especially in kidney,
where they facilate the reabsorbtion of sodium ions
and water from urine.

7. SYNTHESIS OF MINERALOCORTICOIDS
Cholesterol desmolase
3-β hydroxysteroid
dehydrogenase
21-β
hydr
oxyl
ase
Aldosterone Synthase
Cholesterol Pregnenolone Progesterone
21-HydroxyprogesteroneCorticosteroneAldosterone
21-β dehydrogenase

8. Mechanism of Action
 The principle mineralocorticoid action is increase the Na⁺
reabsorption in the distal convoluted tubules in the kidney.
There is an associated increase in the k⁺ and H⁺ excretion.
It’s deficiency results in decreased maximal tubular
reabsorption capacity for Na⁺. So the kidney is not able to
retain Na⁺
 Even in the Na⁺ deficient state it is continuously lost. Then
kidney absorb water without the presence of Na⁺. Which
cause dilutional hyponatraemia
 Excess water enter the cells cellular hydration occur and
also blood volume decreased
 These distortions of fluid and electrolyte balance progress
and contribute to the circulatory collapse. As such these
actions make adrenal cortex essential for survival .

9. Contd….
 Similar action on cation transport is exerted in other
tissues as well. The action of aldosteron is exerted by
gene mediated increased transcription of m-RNA in
renal tubular cells which directs synthesis of proteins
(AIP).
 The Na⁺k⁺ ATPase of tubular basolateral membrane
responsible for generating gradients for movements of
cations . Fig

11. STRUCTURE ACTIVITY RELATIONSHIP

12. Structure Activity Relationship
 The 4,5 double bond and the 3-keto group on ring-A
are essential for mineralocorticoid activity.
 Introduction of additional double bond in the 1,2
position of ring-A increase mineralocorticoid activity.
 Fluorination at the 9-α position on ring-B enhances
mineralocorticoid activity. Fludrocortisone has
enhanced activity or have even greater activity at the
mineralocorticoid receptor.

13. Contd….
 6-α substitution on ring-B has somewhat unpredictable
effects. 6-α methyl cortisol has increased mineralocorticoid
activity but 6-α methylprednisolone has decreased
mineralocorticoid activity.
 An 11-β hydroxyl group on ring-C decreased
mineralocorticoid activity.
 A hydroxyl group at C-21 on ring-D seems to be absolute
requirement for mineralocorticoids activity
 Substitutions at C-16 on ring-D by 9-α fluoro derivatives
(betamethasone, dexamethasone) decreased
mineralocorticoid activity

14. Action
*Excess of aldosterone causes hypokalemia and muscle
weekness and too little aldosterone causes hyperkalemia and
cardiac toxicity
*Excess aldosterone increases tubular (intercalated cell)
hydrogen ion secretion with resultant mild alkalosis
*Aldosterone stimulate sodium and potassium transport in
sweat glands, salivary glands and intestinal epithelial cells
*Excess aldosterone increase ECF volume and arterial
pressure, but has only a small effect on plasma sodium
concentration

15. Marketed Drugs
 Desoxycorticosterone Acetate
 Fludrocortisone Acetate
 Desoxycorticosterone Plvatate
 Desoxinmetasone
 Flurandenolide
 Fluromethalone Acetate

16. REFERENCES
 KD Tripathi., ‘‘Essentials of Medical Pharmacology’’,
Seventh Edition, 2013, Page No-282-284,588
 Thomas L. LEMKE., David A. WILLIAMS., Victoria F.
ROCHE., S.William ZITO., ‘Foye’s Principles of
Medicinal Chemistry’, Sixth Edition, 2010, Wolters
Kluwer(India) Pvt. Ltd., Page No-905-907,885
 D. Sriram., P.Yogeeswari., ‘‘Medicinal Chemistry’’,
Second Edition, Typeset By Ace Pro India Pvt. Ltd.,
Page No-625-626

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