Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy.
J Am Chem Soc
; 140(46): 15764-15773, 2018 11 21.
Article
em En
| MEDLINE
| ID: mdl-30346152
ABSTRACT
The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over their cytotoxic activity would allow improving chemotherapy treatments, and light-regulated drugs are well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor of the human dihydrofolate reductase (DHFR), as a photochromic analogue of methotrexate, a widely prescribed chemotherapeutic drug to treat cancer and psoriasis. Quantification of the light-regulated DHFR enzymatic activity, cell proliferation, and in vivo effects in zebrafish show that phototrexate behaves as a potent antifolate in its photoactivated cis configuration and that it is nearly inactive in its dark-relaxed trans form. Thus, phototrexate constitutes a proof-of-concept to design light-regulated cytotoxic small molecules and a step forward to develop targeted anticancer photochemotherapies with localized efficacy and reduced adverse effects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
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Tetra-Hidrofolato Desidrogenase
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Metotrexato
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Inibidores Enzimáticos
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Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article