Discovery of Novel UV-Filters with Favorable Safety Profiles in the 5-Arylideneimidazolidine-2,4-dione Derivatives Group

Molecules

Dorota Żelaszczyk¹  Henryk Marona¹  Agnieszka Gunia-Krzyżak¹  Ewa Żesławska²  Agata Kryczyk-Poprawa³  Paweł Żmudzki⁴  Kamil Piska⁵  Karolina Słoczyńska⁵  Justyna Popiół⁵  Elżbieta Pękala⁵  Paulina Koczurkiewicz⁵  Katarzyna Wójcik-Pszczoła⁵  Anna Krupa⁶  Wojciech Nitek⁷ 

[1] Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;Department of Chemistry, Institute of Biology, Pedagogical University of Cracow, Podchorążych 2, 30-084 Krakow, Poland;Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;Department of Medicinal Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;Department of Pharmaceutical Technology and Biopharmaceutics, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Krakow, Poland;Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland;

关键词: UV-filters;    UV radiation;    5-arylidenehydantoin derivatives;    photoprotection;    safety evaluation;   

DOI  :  10.3390/molecules24122321

来源: DOAJ

【 摘 要 】

Effective protection from the harmful effects of UV radiation may be achieved by using sunscreens containing organic or inorganic UV filters. The number of currently available UV filters is limited and some of the allowed molecules possess limitations such as systemic absorption, endocrine disruption properties, contact and photocontact allergy induction, and low photostability. In the search for new organic UV filters we designed and synthesized a series consisting of 5-benzylidene and 5-(3-phenylprop-2-en-1-ylidene)imidazolidine-2,4-dione (hydantoin) derivatives. The photoprotective activity of the tested compounds was confirmed in methanol solutions and macrogol formulations. The most promising compounds possessed similar UV protection parameter values as selected commercially available UV filters. The compound diethyl 2,2′-((Z)-4-((E)-3-(4-methoxyphenyl)allylidene)-2,5-dioxoimidazolidine-1,3-diyl)diacetate (4g) was characterized as an especially efficient UVA photoprotective agent with a UVA PF of 6.83 ± 0.05 and favorable photostability. Diethyl 2,2′-((Z)-4-(4-methoxybenzylidene)-2,5-dioxo- imidazolidine-1,3-diyl)diacetate (3b) was the most promising UVB-filter, with a SPF_{in vitro} of 3.07 ± 0.04 and very good solubility and photostability. The main photodegradation products were geometric isomers of the parent compounds. These compounds were also shown to be non-cytotoxic at concentrations up to 50 µM when tested on three types of human skin cells and possess no estrogenic activity, according to the results of a MCF-7 breast cancer model.

【 授权许可】

Unknown