PRODRUGS

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Prodrugs are the molecules that are inactive substances but will get converted into the active substances in our body. Enzymes that are involved in the metabolism are involved in this conversion. The change to active form may take place even chemically. (1)

The exact opposite molecule to the prodrug is the soft drug. Basically these are the drugs that are active and after showing their activity, they will get converted into inactive metabolite which is not toxic to the body. Here we should cover one more definition that is hard drugs, which are the molecules that does not undergo any chemical or metabolic transformation, they remain as they are and so the production of any toxic derivative from the drug is prevented.(1)

Produrgs are generally classified into carrier linked prodrugs and bioprecursor prodrugs. (1,2)

CARRIER LINKED PRODRUGS:

These are the molecules in which a promoiety is present which is generally not required for the activity, but this promoiety is useful in giving the required character to the drug molecule. (1)

By this prodrug concept we can get many desired properties like we can increase the absorption and also the bioavailability.(1,2) We can reduce the toxicity and stability can also be increased.(2)

Generally in maximum cases the promoiety will be lipophilic. (2)

If the promoiety is also having some therapeutic property, then it is called as mutual prodrug.(1)

An example of the mutual prodrug is the estramustine.

BIOPRECURSOR PRODRUGS: (1)

Here there won't be any promoiety, but these contain a functional group that can be metabolized.
Generally oxidation, reduction and phosphorylation are involved.

The principle of oxidation is involved in the nabumetone. Generally the NSAIDS cause gastric irritation. What happens is, generally these drugs are lipophilic in nature and they do not get ionized in the stomach conditions. The gastric pH will be less than the intracellular pH of stomach cells. Since these drugs are lipophilic, they pass into the cells where they get ionized and the H+ return back into the stomach causing damage to the cells. So nabumetone do not have acid functional group and so after absorption it will get converted into the acid in the liver.

The concept of reduction is involved in the mitomycin C. this drug contains the quinone group which cannot show its antineoplastic activity. But this will get converted to hydroquinone that can show the desired activity. The difference is hydroquinone releases the electrons whereas the quinone is electron withdrawing.

The concept of phosphorylation is involved in the antivirals.

References:

1. 1. Wilson and Gisvold Textbook of Organic Medicinal and Pharmaceutical Chemistry, (Produrgs by Forrest T. Smith and C. Randall Clark)edited by John H. Block and John M. Beale, 11th edition, Lippincott Williams& Wilkins Publishers, page no 142 to 154.

2. 2. A text book of Medicinal Chemistry by Surendra nath Pandey, Volume 1, SG Publishers, page no 54 & 55.

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Author: Siva Mavuduru

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