[SagarikaGhosh]

There are a variety of approaches for drug designing. The below mentioned approach aims at designing drugs, which specifically and selectively fit into the critical sites of the target molecules, thereby inactivating the latter. The target molecule may be a receptor, an enzyme, ion channel, DNA, nuclear receptor etc.

The aim of drug designing is to develop highly efficient drug, which have little or no side effects. There are three main steps in drug designing- detailed knowledge ( including the 3D structure ) of the critical sites of target molecules, designing of drug molecules and evaluation of the interaction of the synthesized drugs with the target molecules and further modifications to make them safe for medicinal use.

The general procedure for drug designing may be illustrated by the development of antihypertensive drug captopril. The lead for this drug came from the observation that when South American pit viper ( Bothrops jaraca) bites its prey, the latter faints and ultimately dies due to rapid fall in its blood pressure. In humans, regulation of BP is relatively complex, but angiotensin II (an octapeptide) plays the key role in increasing BP. Angiotensin II is produced from angiotensin I by removal of two amino acids by angiotensin converting enzyme (ACE). It was then discovered that the ACE was not available, but much was known about the active site of a similar enzymes, caboxypeptidase A; both the enzymes are zinc containing peptidases. This knowledge was used to synthesize molecules that would specifically bind the active site of ACE and thereby inhibit its enzyme action and block the production of angiotensin II. One molecule, out of the large number of molecules synthesized and sequentially evaluated in cell-free in vitro assays, cell- based activity tests, animal trials and finally, in clinical trials, was developed into the successful antihypertensive drug captopril. The knowledge of captopril design triggered the development of a series of substitute antihypertensive drugs.