New cytokinin derivatives possess UVA and UVB photoprotective effect on human skin cells and prevent oxidative stress

0489495 - ÚEB 2019 RIV FR eng J - Journal Article
Hönig, Martin - Plíhalová, Lucie - Spíchal, L. - Grúz, Jiří - Kadlecová, Alena - Voller, Jiří - Rajnochová Svobodová, A. - Vostálová, J. - Ulrichová, J. - Doležal, Karel - Strnad, Miroslav
New cytokinin derivatives possess UVA and UVB photoprotective effect on human skin cells and prevent oxidative stress.
European Journal of Medicinal Chemistry. Roč. 150, APR 25 (2018), s. 946-957. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MŠMT(CZ) LO1204
Institutional support: RVO:61389030
Keywords : Aromatic cytokinins * Caenorhabditis elegans * Kinetin derivatives * Oxidative stress * UVA/UVB photoprotectivity
OECD category: Biochemistry and molecular biology
Impact factor: 4.833, year: 2018

Eleven 6-furfurylaminopurine (kinetin, Kin) derivatives were synthesized to obtain biologically active compounds. The prepared compounds were characterized using 1 H NMR, mass spectrometry combined with HPLC purity determination and elemental C, H, N analyses. The biological activity of new derivatives was tested on plant cells and tissues in cytokinin bioassays, such as tobacco callus, detached wheat leaf chlorophyll retention bioassay and Amaranthus bioassay. The selected compounds were subsequently tested on normal human dermal fibroblasts (NHDF) and keratinocyte cell lines (HaCaT) to exclude possible phototoxic effects and, on the other hand, to reveal possible UVA and UVB photoprotective activity. The protective antioxidant activity of the prepared cytokinin derivatives was further studied and compared to previously prepared antisenescent compound 6-furfurylamino-9-(tetrahydrofuran-2-yl)purine (Kin-THF) using induced oxidative stress (OS) on nematode Caenorhabditis elegans damaged by 5-hydroxy-1,4-naphthoquinone (juglone), a generator of reactive oxygen species. The observed biological activity was interpreted in relation to the structure of the prepared derivatives. The most potent oxidative stress protection of all the prepared compounds was shown by 6-(thiophen-2-ylmethylamino)-9-(tetrahydrofuran-2-yl)purine (6) and 2-chloro-6-furfurylamino-9-(tetrahydrofuran-2-yl)purine (9) derivatives and the results were comparable to Kin-THF. Compounds 6 and 9 were able to significantly protect human skin cells against UV radiation in vitro. Both the derivatives 6 and 9 showed higher protective activity in comparison to previously known structurally similar compounds Kin and Kin-THF. The obtained results are surprising due to the fact that the prepared compounds showed to be inactive in the ORAC assay which proved that the compounds did not act as direct antioxidants as they were unable to directly scavenge oxygen radicals.
Permanent Link: http://hdl.handle.net/11104/0283905