Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland.
Molecules. 2022 Mar 12;27(6):1850. doi: 10.3390/molecules27061850.
This study aimed to assess two novel 5-arylideneimidazolidine-2,4-dione (hydantoin) derivatives (JH3 and JH10) demonstrating photoprotective activity using the reconstructed human skin model Episkin. The skin permeability, irritation, and phototoxicity of the compounds was evaluated in vitro. Moreover, the in vitro genotoxicity and human metabolism of both compounds was studied. For skin permeation and irritation experiments, the test compounds were incorporated into a formulation. It was shown that JH3 and JH10 display no skin irritation and no phototoxicity. Both compounds did not markedly enhance the frequency of micronuclei in CHO-K1 cells in the micronucleus assay. Preliminary in vitro studies with liver microsomes demonstrated that hydrolysis appears to constitute their important metabolic pathway. Episkin permeability experiments showed that JH3 permeability was lower than or close to currently used UV filters, whereas JH10 had the potential to permeate the skin. Therefore, a restriction of this compound permeability should be obtained by choosing the right vehicle or by optimizing it, which should be addressed in future studies.
本研究旨在评估两种具有光保护活性的新型 5-芳亚甲基咪唑烷-2,4-二酮（海因）衍生物（JH3 和 JH10），使用重建的人体皮肤模型 Episkin。在体外评估了化合物的皮肤渗透性、刺激性和光毒性。此外，还研究了这两种化合物的体外遗传毒性和人体代谢。对于皮肤渗透和刺激性实验，将测试化合物掺入配方中。结果表明，JH3 和 JH10 无皮肤刺激性，无光毒性。在微核试验中，这两种化合物均未明显增加 CHO-K1 细胞中微核的频率。初步的体外肝微粒体研究表明，水解似乎是它们的重要代谢途径。Episkin 渗透实验表明，JH3 的渗透性低于或接近目前使用的 UV 滤光剂，而 JH10 有可能穿透皮肤。因此，应通过选择合适的载体或对其进行优化来限制该化合物的渗透性，这将在未来的研究中解决。
