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Drug Designing to Produce Designer Drugs - ashwathi - 10-28-2012
Drug designing is a process of constructing ailments specific drugs adopting the known properties of diseases applying different technologies.
Small organic molecules which bind and modulate the properties of specific biological receptors or targets is known as drugs. These receptors are mostly protein molecules which perform several important functions and are vital for the proper functioning of the cell. In case of abnormalities, these receptors get affected and are reflected as minor or major physical symptoms. Drugs acts to alter the defective receptors to restore its actual functions helping in treating the symptoms.
Drug Designing :
The process of constructing ailments specific drugs adopting the known properties of diseases applying different technologies is known as drug designing. This aims at designing drugs which can specifically and selectively bind to the target sites thereby modifying the same. Drug designing techniques employing computer based techniques is known as computer-aided drug design and those based on the information on the three dimensional structure of targets is known as structure– based design.
Tasks involved in drug designing:
(i) Analyse medical condition to determine the target site.
(ii) In-depth knowledge of the critical sites of target molecules.
(iii) Designing of drugs which specifically target the receptor molecules.
(iv) Synthesis and administration of drugs.
(v) Assessment of the drug-target interaction and record of the same.
(vi) Execute any necessary modification required.
Successful examples of drug designing:
Propanolol: It is one of the successful examples in drug designing.This drug is used as a treatment against heart attacks and hypertension. The heart ailments are mostly caused by excess amount of epinephrine and norepinephrine hormones. Both these hormones consist of alpha and beta receptors. The propanolol is so designed so that it binds with the beta receptors inactivating the hormones.
Cimetidine: This drug is useful in the treatment of stomach ulcers. In stomach ulcers, there is excess release of Hcl into the stomach induced by the histamine. Cimetidine blocks the binding of histamine to its H2 receptor present in the stomach lining blocking the Hcl release and thus cures the ulcer.
Drug delivery:
After a drug has been designed the next major step involved is the delivery of the drugs into the system. The normal routes of drug delivery are oral or parenteral. While following these common methods, drug delivery is not specific as it is distributed over the whole body. This demand administration of higher doses and may not always evoke a positive response. Other complications are proteolytic degradation of orally administered protein drugs, less permeability of such drugs owing its larger structure. As a result various other mechanisms have been developed for more efficient delivery of drugs:
(i) Delivery by alternative routes- other routes such as nasal, vaginal, anal, ocular, etc can be used while using protein based drugs. In order to improve the efficiency of such delivery, permeability enhancers to improve the permeability of drugs can be used. Commonly used enhancers are sodium deoxycholate, sodium glycocholate etc
(ii) Liposomes- these are artificially composed lipid vesicles. Drugs can be encapsulated in liposome and administered. Tissue specificity of liposome can be accentuated by use of specific surface ligands.
(iii) Polymers: Polymers, which are biodegradable, have been used extensively for successful delivery of drug; the drug is released by cleavage of drug fro polymer. This procedure is used for slow release of drugs of larger size.
(iv) Drug targeting: the procedure involving site directed delivery of drugs is known as drug targeting
Drug targeting
It is one of the most effective mechanisms involved in delivery of drugs to specific location or specific targets. The principle of such a mechanism is based on monoclonal antibodies.
In monoclonal antibodies, all the antibodies present in one single preparation reacts specifically with only one target. This property aids in drug targeting. The most widespread application in the use of monoclonal antibodies in this context is as immunotoxins. Monoclonal antibodies are linked with a toxin polypeptide to form immunotoxins. The target specific antibodies ensure selective and specific binding and the toxin in the immunotoxins inactivates or kills the targets.
Ricin: an example of immunotoxins and drug targeting tumour cells
The natural toxin ricin is isolated from endosperm of castor. It consists of two polypeptide chains called as A and B where the polypeptide A accounts for its toxicity. The immunotoxin formed as a conjugate between an antibody and ricin A chain results in specific binding to tumour cells and irreversible enzymatic modification of ribosomes preventing protein synthesis is such cells.
RE: Drug Designing to Produce Designer Drugs - SagarikaGhosh - 08-20-2013
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.