Structural studies on antifolate drugs.
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Structural studies on antifolate drugs. by Patrick Kevin Bryant

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Published by Aston University. Department of Pharmaceutical Sciences in Birmingham .
Written in English


Book details:

Edition Notes

Thesis (Phd) - Aston University, 1988.

ID Numbers
Open LibraryOL13876207M

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These structural differences from folic acid confer on these analogs an extremely high affinity for DHFR. The primary action of aminopterin and methotrexate (MTX), the “classical” antifolates, is the inhibition of this enzyme. The 4-amino antifolates are among the most potent enzyme inhibitors known. The antifolates remain a topic of continuing fascination to pharmacologists. This in-terest is not entirely theoretical. Recent years have seen two new antifolate drugs approved for marketing: trimetrexate (Neutrexin), a lipophilic inhibitor of dihydrofolate reductase (DHFR) for treatment of the life-threatening fungal infection, Pneumocystis carinii pneumonia; and the thymidylate synthase (TS) inhibitor, raltitrexed (Tomudex), for colorectal cancer.   Antifolate drugs are used as antimalarials through their inhibition of folate metabolism of the parasite, both in the synthesis and use of folate cofactors. Humans do not make any folate cofactors, relying only on exogenous supply, and are therefore mostly spared from the effects of antifolate drugs. The key enzyme targets are dihydropteroate synthase (DHPS), inhibited by sulfa drugs, and . Antifolate drugs are molecules directed to interfere with the folate metabolic pathway at some level. They can be recognized among the first rationally designed compounds applying the principle of structural analogy with the substrate developing the antimetabolite strategy.

Chemical structures of methotrexate and other diaminopteridine derivatives. The binding mode of methotrexate is highly conserved in PTR enzymes as demonstrated by the structural characterization of the complexes with Lm PTR1 (PDB id 1E7W), 9 Tc PTR2 (PDB id 1MXF), 13 and Tb PTR1 (PDB id 2C7V) 12 (Fig. 6). In Antifolate Drugs in Cancer Therapy, Ann Jackman and a panel of highly regarded researchers comprehensively review the current status of novel antifolates, an important class of anticancer drugs. The distinguished contributors discuss the preclinical and clinical pharmacology of methotrexate, other dihydrofolate reductase inhibitors.   Antifolate drug development has focused on agents designed to overcome different aspects of methotrexate resistance. This article reviews the enzymatic targets for antifolates, describes the known mechanisms of antifolate resistance, and summarizes the current development of novel antifolate by: Novel antifolate drugs. due to the structural similarity of MTX with FA and presence of FA receptor as targeting ligand on the surface of the was attributed to study drug in one patient.

Europe PMC is an Elixir Core Data Resource Learn more ›. Europe PMC is a service of the Europe PMC Funders' Group, in partnership with the European Bioinformatics Institute; and in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine (NCBI/NLM).It includes content provided to the PMC International archive by participating : Patrick K. Bryant. In Antifolate Drugs in Cancer Therapy, Ann Jackman and a panel of highly regarded researchers comprehensively review the current status of novel antifolates, an important class of anticancer drugs. The distinguished contributors discuss the preclinical and clinical pharmacology of methotrexate. In Antifolate Drugs in Cancer Therapy, Ann Jackman and a panel of highly regarded researchers comprehensively review the current status of novel antifolates, an important class of anticancer drugs. Structural studies on antifolate drugs Author: supporting and enhancing data obtained in the lower resolution studies of protein crystallography. The biological importance of these compounds is discussed and an attempt is made to relate/predict their pharmacological activity to observed structural features in the crystalline environment Author: Patrick K. Bryant.