Development of new drugs is a time-consuming, hugely expensive and an uncertain endeavor.
The pharmaceutical industry is looking for cost-effective alternatives with reduced risks of
drug failure. Validated target machinery along with established inhibitors indicates usefulness in drug
design, discovery and further development. Folate metabolism, found in both prokaryotes and eukaryotes,
represents an essential druggable target for chemotherapy. Numerous enzymes in the cell
replication cycle use folate either as a cofactor or as a substrate. DHFR, an enzyme of the folate biosynthesis
pathway is an established chemotherapeutic target, initially explored for anti-cancer drug discovery. Diaminopteridines
e.g. methotrexate and aminopterin, primarily used as anti-cancer agents, are folic acid analogues, first reported in
late 1940’s, used to produce temporary remission of acute leukaemia in children. However, due to the toxicity of these
drugs, they could not be used for other therapeutic implications such as in the treatment of infectious diseases. Development
of newer diaminopteridine derivatives has helped in repositioning their therapeutic usefulness. These analogues have
now been proven as anti-parasitic, immuno-suppressants, anti-bacterial agents, to enlist a few therapeutic applications.
Likewise, diaminopyrimidine, diaminoquinazoline and diaminodihydrotriazines are being explored for structural modifications
by which they can be repurposed from their originally developed medicinal applicability and exploited for various
other infectious disease conditions. In this review, we encompass the study of DHFR inhibitors potentially to be repurposed
for different infectious disease case scenario and also highlight the novel anti-infective drug discovery benefits