Tapinarof and its structure-activity relationship for redox chemistry and phototoxicity on human skin keratinocytes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F24%3A43908430" target="_blank" >RIV/60076658:12310/24:43908430 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/24:73627103 RIV/61989592:15310/24:73627103
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0891584924005781?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0891584924005781?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.freeradbiomed.2024.07.032" target="_blank" >10.1016/j.freeradbiomed.2024.07.032</a>
Alternative languages
Result language
angličtina
Original language name
Tapinarof and its structure-activity relationship for redox chemistry and phototoxicity on human skin keratinocytes
Original language description
Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA (R)). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The pKa value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox >= resveratrol > pterostilbene > tapinarof > pinosylvin >> pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4 '-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315-399 nm) radiation. In aqueous media at pH 7.4, we observed an similar to 50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 mu M, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Free Radical Biology and Medicine
ISSN
0891-5849
e-ISSN
1873-4596
Volume of the periodical
223
Issue of the periodical within the volume
OCT 2024
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
212-223
UT code for WoS article
001294474800001
EID of the result in the Scopus database
2-s2.0-85200807345