Bencze Flórián, Kiss László, Li Heng, Yan Hui, Kollár László, Kunsági-Máté Sándor
Institute of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Pécs, Honvéd útja 1, H-7624 Pécs, Hungary.
Department of Physical Chemistry and Materials Science, Faculty of Sciences, University of Pécs, Ifjúság útja 6, H-7624 Pécs, Hungary.
Int J Mol Sci. 2024 Nov 26;25(23):12703. doi: 10.3390/ijms252312703.
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 configuration of phototrexate is bioactive, in this work, the effect of the molecular environment on the stability of the 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 conversion and enhanced stabilities of the isomer in methanol. Temperature-dependent measurements of the isomerization rate reflect the increased activation energy in methanol.
抗癌药物光氨蝶呤是抗代谢物二氢叶酸还原酶抑制剂甲氨蝶呤的一种可光切换衍生物，其治疗适用性高度依赖于其生物活性异构体的稳定性。鉴于只有光氨蝶呤的 构型具有生物活性，在本研究中，研究了分子环境对该药物 异构体稳定性的影响。采用了紫外-可见吸收和基于荧光的溶剂弛豫方法。质子性甲醇和非质子性二甲亚砜被用作中程介电常数溶剂。结果表明，在甲醇中， 转化速率降低， 异构体的稳定性增强。对异构化速率进行的温度依赖性测量反映出在甲醇中活化能增加。
