2021
DOI: 10.1002/slct.202102555
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An Insight into Synthetic Strategies and Recent Developments of Dihydrofolate Reductase Inhibitors

Abstract: The dihydrofolate reductase (DHFR) is a significant target in cancer, microbial infection, fungal infection, malaria, leishmaniasis, and tuberculosis, among other diseases. The DHFR gene was discovered in prokaryotes and eukaryotes in the late 1950s and is found in all dividing cells. DHFR inhibitors are used for a variety of medicinal purposes. Increased resistance to therapeutic agents such as anticancer, antibiotic, anti‐tuberculosis, and antifungal sparked interest in the development of potent, broad‐spect… Show more

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Cited by 16 publications
(9 citation statements)
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References 86 publications
(45 reference statements)
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“…Some of the N‐heterocyclic containing EGFR inhibitor approved by the US FDA are shown in Figure 5 [44,59] . Moreover, N‐heterocyclic compounds exhibit different biological properties such as anti‐HIV, antidiabetic, herbicidal activity, anticancer activity, insecticidal agents, anti‐inflammatory, [60] antibacterial, [41b] antioxidant, [44,61] anticonvulsant, [58b,62] antiallergic, and enzyme inhibitors. These N‐heterocyclic rings also meet the fundamental pharmacophore which is a prerequisite requirement for any molecule to be an EGFR inhibitor.…”
Section: Importance Of Nitrogen Containing Heterocyclic Compound As E...mentioning
confidence: 99%
“…Some of the N‐heterocyclic containing EGFR inhibitor approved by the US FDA are shown in Figure 5 [44,59] . Moreover, N‐heterocyclic compounds exhibit different biological properties such as anti‐HIV, antidiabetic, herbicidal activity, anticancer activity, insecticidal agents, anti‐inflammatory, [60] antibacterial, [41b] antioxidant, [44,61] anticonvulsant, [58b,62] antiallergic, and enzyme inhibitors. These N‐heterocyclic rings also meet the fundamental pharmacophore which is a prerequisite requirement for any molecule to be an EGFR inhibitor.…”
Section: Importance Of Nitrogen Containing Heterocyclic Compound As E...mentioning
confidence: 99%
“…Owing to the growing drug resistance to some of the available DHFR inhibitors, research for the discovery of new and selective DHFR inhibitors has been intensely increased, using molecular modeling, synthetic techniques, in vivo and in vitro biological investigation, mechanistic studies, and structure-activity relationships [ 10 , 11 , 12 ].…”
Section: Introductionmentioning
confidence: 99%
“…DHFR is an important target in cancer, microbial infections, malaria, tuberculosis, fungal infections etc. [5]. DHFR is involved in the folate synthetic pathway responsible for DNA synthesis which is initiated by the cellular uptake of folic acid through a specialized mechanism followed by the reduction of dihydrofolate to tetrahydrofolate (THF) in the presence of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) [3].…”
Section: Introductionmentioning
confidence: 99%