Antibacterials pp 123-149 | Cite as

The Antifolates

Part of the Topics in Medicinal Chemistry book series (TMC, volume 26)


Cells rely on the synthesis of essential metabolites to ensure proper cell function, growth, and survival. Folate biosynthesis is a ubiquitous pathway found in organisms and is responsible for the generation of thymidine, methionine, histidine, and purines. Drugs that target essential enzymes along this pathway have been known since the 1930s as having clinical utility as antibacterial, anticancer, antimalarial, and antifungal agents. These drugs are commonly referred to as antifolates. However, bacterial resistance mechanisms against the antibacterial antifolates have emerged that have rendered many of these antifolates as unsuitable treatment options, and threaten those antifolates that are still used today. Here we describe the history of the drugs that target the essential enzymes in folate biosynthesis, the bacterial resistance mechanisms that have emerged to limit their use, and the current strategies that are being employed to overcome the prevalent resistance mechanisms.


Dihydrofolate reductase Dihydropteroate synthase Iclaprim Propargyl-linked antifolates Sulfonamides Trimethoprim 


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© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  1. 1.School of PharmacyUniversity of ConnecticutStorrsUSA

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