Current Pharmaceutical Design - Volume 9, Issue 31, 2003

Antimetabolites are structural analogs of naturally occurring compounds. Antimetabolites interfere with the production of nucleic acids. They work through a variety of mechanisms including competition for binding sites on enzymes and incorporation into nucleic acids. The FdUMP metabolite of 5-FU can even act as a suicide inhibitor of thymidylate synthase. Some antimetabolites are prodrugs, i.e., they must be biochemically co Read More

The viral enzyme, HIV integrase (MW 32 kDa), is one of the three key enzymes of the pol gene of HIV. HIV integrase is involved in the integration of HIV DNA into host chromosomal DNA. There is apparently no functional equivalent of this enzyme in human cells. Integration of HIV DNA into the host cell genome apparently occurs by a carefully defined sequence of DNA tailoring (3'-processing) and coupling (joining or integration) Read More

Acyclic nucleoside phosphonates (ANP) are analogs of nucleotides exhibiting various biological (e.g. antiviral, cytostatic, antiparasitic, immunomodulatory) activities. This review describes synthetic approaches to their preparation, biological activities, structure-activity relationships and mode of action of ANPs, with emphasis to selected drugs or drug candidates. Three compounds of the ANP group (cidofovir, adefovi Read More

Antifolates are the oldest of the antimetabolite class of anticancer agents and were one of the first modern anticancer drugs. The first clinically useful antifolate, described in 1947, was 2,4-diamino-pteroylglutamate (4-amino-folic acid; aminopterin; AMT) which yielded the firstever remissions in childhood leukemia. AMT was soon superseded by its 10-methyl congener, methotrexate (MTX), based on toxicity considerations; MTX Read More

Derivatives of the vitamin folic acid function in the body for the synthesis of thymidylate, purines and amino acids and are necessary for normal metabolism and growth. Methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR) is the outstanding example of an antitumor antifolate. MTX is clinically useful in the treatment of childhood leukemia, choriocarcinoma and psoriasis, where it corrects abnormal growth, and i Read More

6-Mercaptopurine (6MP) and 6-thioguanine (6TG) are analogs of the natural purines: hypoxanthine and guanine. Both mercaptopurine and thioguanine are substrates for hypoxanthineguanine phosphoribosyltransferase and are converted into the ribonucleotides 6-thioguanosine monophosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) respectively. The accumulation of these monophosphates inhibits Read More