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Effect of the Protic vs. Non-Protic Molecular Environment on the cis to trans Conformation Change of Phototrexate
Flórián Bencze1,2, László Kiss1,3, Heng Li4,5
1Institute of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pécs, Honvéd útja 1, H-7624 Pécs, Hungary.
Abstract:
The therapeutical applicability of the anticancer drug phototrexate, a photoswitchable derivative of the antimetabolite dihydrofolate reductase inhibitor methotrexate, highly depends on the stability of its bioactive isomer. Considering that only the cis configuration of phototrexate is bioactive, in this work, the effect of the molecular environment on the stability of the cis isomer of this drug has been investigated. UV-vis absorption and fluorescence-based solvent relaxation methods have been used. Protic methanol and non-protic dimethylsulfoxide were used as medium-ranged permittivity solvents. The results showed a decreased rate of cis → trans conversion and enhanced stabilities of the cis isomer in methanol. Temperature-dependent measurements of the isomerization rate reflect the increased activation energy in methanol.
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