Singlet oxygen production and in vitro phototoxicity studies on fenofibrate, mycophenolate mofetil, trifusal, and their active metabolites

"This is the peer reviewed version of the following article: Molins-Molina, Oscar, Roger Bresolí-Obach, Guillermo Garcia-Lainez, Inmaculada Andreu, Santi Nonell, Miguel A. Miranda, and M. Consuelo Jiménez. 2017. Singlet Oxygen Production and in Vitro Phototoxicity Studies on Fenofibrate, Mycophenolate Mofetil, Trifusal, and Their Active Metabolites. Journal of Physical Organic Chemistry 30 (9). Wiley: e3722. doi:10.1002/poc.3722, which has been published in final form at https://doi.org/10.1002/poc.3722. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."
[EN] Singlet oxygen photosensitization (studied by time-resolved near-infrared emission spectroscopy) and in vitro phototoxicity (by means of the 3T3 neutral red uptake assay) have been investigated for the prodrugs fenofibrate (FFB), mycophenolate mofetil (MMP), and trifusal (TFS) as well as for their active metabolites fenofibric acid (FFA), mycophenolic acid (MPA), and 2-hydroxy-4-(trifluoromethyl) benzoic acid (HTB). The results show that FFB and its active metabolite FFA generate O-1(2) with a quantum yield in the range 0.30 to 0.40 and show a photo-irritation factor (PIF) higher than 40. By contrast, MMP/MPA and TFS/HTB are not photoactive in the used assays. These results correlate well with the previously reported in vivo phototoxicity in treated patients.