DHFA, 7,8-dihydrofolic

The folate pathway is one in which selective chemotherapeutic intervention has been very successful, and a number of drugs acting through this pathway are in current use. This is because of the fact that mammals receive FA from their diet and convert it into dihydrofolic acid (DHFA) and tetrahydrofolic acid (THFA), which give rise to folate cofactors. The bacteria and protozoans, on the other hand can not effectively utilize FA to get their requirements of DHFA and THFA. Consequently, these organisms synthesize DHFA de novo (for details, see Chapter 13). Further the affinity of the enzymes involved from different sources (mammalian, bacterial and protozoan) for different classes of inhibitors is quite different, which has resulted in the development of drugs with selective action. 

The key enzymes involved in the biosynthesis of DHFA and THFA are dihy-dropteroate synthetase, dihydrofolate synthetase and dihydrofolate reductase [1-3]. Drugs that block the synthesis of dihydropteroic acid are known as dihydropteroate synthetase inhibitors (PABA antagonists) and those which control the reduction of DHFA to THFA are called dihydrofolate reductase (DHFR) inhibitors. Collectively these drugs are known as antifolates. 

For the assay of dihydrofolate reductases (see p 612) suspend 66.5mg of DHFA in lOmL of O.OOIM HCl containing lOmM dithiothreitol (DTT stock made from 154mg in lOmL H2O making O.IM), shake well and freeze in 400 total volume of 2mL) to give a clear solution. To estimate the concentration of DHFA in this solution, dilute... 

Dihydrofolic acid (7,8-dihydropteroyl-L-glutamic acid, DHFA) [4033-27-6] M 443.4, pKj 2.0 (basic... 

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