Structure activity Relationship of Drugs

STRUCTURE ACTIVITY RELATIONSHIP (SAR)

Drug activity is intimately related to its chemical structure. This is called a structure-activity relationship.

The chemical structure of a drug is useful for certain purposes

They were listed below:

(a) To achieve more target actions, synthesize new compounds with few adverse reactions.

(b) For the synthesis of competitive antagonists.

Most of the vital drugs are obtained from natural sources (plant sources) like morphine, quinine, atropine, etc. The study of the chemical structures of the other products with their respective medicinal properties furnished useful information regarding the relationship between the chemical structure and activity. By this study it can be concluded that the biological activity of a compound is associated with a specific structural unit or group known as "PHARMACOPHORE" In a compound, if a particular pharmacophore group is absent then the compound loses its activity.

The relationship between the chemical structure and biological activity is illustrated by the following examples:

1. Procaine

Procaine is an example of a local anaesthetic which produces local anaesthesia when infiltrated beneath the skin. when the same drug is administered through the IV route, it reduces the rate and the excitability of the myocardium. But, the major problem is, that it gets rapidly hydrolysed (chemically it is an ester). Therefore, a compound structurally much similar to procaine and resistant to hydrolysis is synthesized and it is procainamide. it is the most widely used drug in the management of cardiac arrhythmias.

The following are the structures of procaine and procainamide:

Procaine (local anaesthetic)

Procainamide (antiarrhythmic drug)

2.Atropine

When installed into the eye, the alkaloid, atropine produces the dilatation of the pupil and cycloplegia. This dilatation of the pupil and cycloplegia persist for about one week. to reduce the problem, a substitute known as homatropine was synthesized. This is not having the side effects of the parent compound (atropine).

The structures of atropine and homatropine are:

atropine

Homatropine

3.Chlorpromazine

Chlorpromazine drug possesses a combination of pharmacological actions such as antihistaminic, anticholinergic, hypotensive, and antipsychotic. Chlorpromazine is an example of a phenothiazine derivative. By slight structural modification. another drug known as trifluoperazine is synthesized. this drug has mainly antipsychotic activity with very little antihistaminic or hypotensive activities. the structures of chlorpromazine and trifluoperazine are :

Chlorpromazine

Trifluoperazine

4. Niacin

Niacin or nicotinic acid is an example of a compound used in the management of pellagra. But the problem with these drugs is that they produce itching and flushing of the skin. A structurally relative compound known as nicotinamide is having the same biological activity with less bad effects of niacin.

These are the structures of niacin and nicotinamide:

Niacin and Nicotinamide both are the same in structure

5. Benzylpenicillin

Benzylpenicillin is an antibiotic, and it cannot be administered by mouth. the reason is, it gets inactivated in the stomach by gastric hydrochloric acid. Therefore, to avoid this drawback, penicillins that can be taken by mouth are developed with few structural changes.

Ex: Phenoxymethylpenicillin.

This is not inactivated in the stomach.

Structures of Benzylpenicillin and Phenoxymethyl penicillin :

Benzylpenicillin (not for oral administration)

Phenoxymethyl penicillin (for oral administration)

6. PABA

Para-aminobenzoic acid (PABA) is a vital growth factor and it's essential for the growth of several micro-organisms. Para aminosalicylic acid (PAS) is an example of an anti-tubercular drug. PAS shows structural similarity to PABA, probably acts by competing with PABA for the uptake by bacteria. Lack of PABA in the bacteria leads to the arrest of growth and multiplication of bacteria. the structures of PABA and PAS are :

PABA

PAS

7. Chlorpromazine

This drug is an example of a tranquillizer mainly used in the management of psychotic disorders (antipsychotic). Imipramine, a structurally related drug, on the other hand, is an antidepressant (mood elevator)

The following are the structures of these 2 drugs: