Journal
MOLECULES
Volume 24, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/molecules24061140
Keywords
dihydrofolate reductase (DHFR) enzyme; DHFR inhibitors as anticancer agents; heterocyclic compounds; DHFR drug discovery; hybrid compounds
Funding
- Ministero dell'Istruzione dell'Universita e della Ricerca (MIUR) of the Italian Government [PJ_ RIC_ FFABR_ 2017_ 160599]
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Dihydrofolate reductase inhibitors are an important class of drugs, as evidenced by their use as antibacterial, antimalarial, antifungal, and anticancer agents. Progress in understanding the biochemical basis of mechanisms responsible for enzyme selectivity and antiproliferative effects has renewed the interest in antifolates for cancer chemotherapy and prompted the medicinal chemistry community to develop novel and selective human DHFR inhibitors, thus leading to a new generation of DHFR inhibitors. This work summarizes the mechanism of action, chemical, and anticancer profile of the DHFR inhibitors discovered in the last six years. New strategies in DHFR drug discovery are also provided, in order to thoroughly delineate the current landscape for medicinal chemists interested in furthering this study in the anticancer field.
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