Photoswitchable Antimetabolite for Targeted Photoactivated Chemotherapy

• DOI: 10.1021/jacs.8b08249
• Publication Date: 2018-10-10T19:35:51Z
• Authors: Carlo Matera; Alexandre M. J. G...; Núria Camarero; Michela Libergoli; Concepció Soler; Pau Gorostiza
• Keywords: Dihydrofolate reductase; Antifolate

The efficacy and tolerability of systemically administered anticancer agents are limited by their off-target effects. Precise spatiotemporal control over cytotoxic activity would allow improving chemotherapy treatments, light-regulated drugs well suited to this purpose. We have developed phototrexate, the first photoswitchable inhibitor human dihydrofolate reductase (DHFR), as a photochromic analogue methotrexate, widely prescribed chemotherapeutic drug treat cancer psoriasis. Quantification DHFR enzymatic activity, cell proliferation, in vivo effects zebrafish show that phototrexate behaves potent antifolate its photoactivated cis configuration it is nearly inactive dark-relaxed trans form. Thus, constitutes proof-of-concept design small molecules step forward develop targeted photochemotherapies with localized reduced adverse