1. Captopril
Md.Rafsani Alam Ananda
1631182049

2. Captopril
Captopril is a sulfhydryl-containing analogue of proline
with antihypertensive activity & antineoplastic activity.
Captopril is a specific competitive inhibitor of angiotensin
I-converting enzyme (ACE) that enzyme responsible for the
conversion of angiotensin I to angiotensin II. Captopril is a
white to off-white crystalline powder that may have a
slight sulfurous odor; it is soluble in water ,methanol, &
ethanol and sparingly soluble in chloroform and ethyl
acetate

3. Discovery of Captopril
One of the first drugs marketed for lowering blood pressure
was found by studying the venom from Bothrops jararaca, a
poisonous snake. Captopril, an analog of the snake venom's
ACE-inhibiting peptide, was first synthesized in 1975 by three
researchers at the U.S. drug company E.R. Squibb & Sons
Pharmaceuticals. The development of captopril was among
the earliest successes of the revolutionary concept of ligand-
based drug design.

4. Mechanism of action
Captopril prevents the conversion of angiotensin I to
angiotensin II by inhibition of ACE.
 Decreased plasma angiotensin II.
 Increased plasma renin activity resulting from loss of
negative feedback on renin release.
Decreased aldosterone secretion.
Small increases in serum potassium with sodium and
fluid loss.

5. Active site of Captopril
 The thiol (SH) group of captopril makes direct
interaction with Zn2+
The carbonyl group forms strong hydrogen
bonding with two histidines
The carboxylate group interacts with a cationic
group on the enzyme
The proline and the methyl are involved in a
stereospecific hydrophobic and van der Waals
interactions

6. Development of Captopril & its Analogues
The substituent of the acyl group might
also influence binding to the enzyme.
Methyl substituent was found to enhance
the inhibitory potency by about 15 fold.
Replacement of the nitrogen containing
functionalities did not enhance inhibitory
activity.
Potency increase by the replacement of the
carboxyl group with a sulfhydryl function (SH)

7. Pharmacokinetics of Captopril
Captopril rapidly absorbed and has a
bioavailability of about 75% (oral).
Peak concentrations in plasma occur within an
hour, and the drug is cleared rapidly with a
half-life of approximately 2 hours

8. Clinical Use
Treatment of hypertension.
Treatment of heart failure.
Secondary prevention after
myocardial infarction.
Diabetic nephropathy in insulin-
dependent diabetes mellitus.

9. Marketed Captopril in Bangladesh

10. Adverse effects
Dizziness
Loss of taste.
Dry cough
Headache
Hyperkalemia
Teratogenicity
Acute renal failure
Leukopenia
Contraindication :
Hypersensivity,stenosis,renal
impairment,pregnancy.

11. Optimization of Captopril
Captopril has the metallic taste problem,
medicinal chemists proposed the use of
carboxylate, instead of sulfhydryl, as the
Zn binding group.