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.

Raimondi, M.V., Randazzo, O., Franca, M.L., Barone, G., Vignoni, E., Rossi, D., et al. (2019). DHFR inhibitors: Reading the past for discovering novel anticancer agents [10.3390/molecules24061140].

DHFR inhibitors: Reading the past for discovering novel anticancer agents

Raimondi, Maria Valeria
;
RANDAZZO, Ornella;Franca, Mery La;Barone, Giampaolo;
2019-01-01

Abstract

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.
2019
Settore CHIM/08 - Chimica Farmaceutica
Settore CHIM/03 - Chimica Generale E Inorganica
Raimondi, M.V., Randazzo, O., Franca, M.L., Barone, G., Vignoni, E., Rossi, D., et al. (2019). DHFR inhibitors: Reading the past for discovering novel anticancer agents [10.3390/molecules24061140].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/351202
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