Evaluation of toxicological aspects of three new benzoxazole compounds with sunscreen photophysical properties using in silico and in vitro methods

Toxicol In Vitro. 2022 Mar:79:105300. doi: 10.1016/j.tiv.2021.105300. Epub 2021 Dec 18.

Abstract

Sunscreening chemicals protect against damage caused by sunlight most absorbing UVA or UVB radiations. In this sense, 2-(2'-hydroxyphenyl)benzoxazole derivatives with amino substituents in the 4' and 5' positions have an outstandingly high Sun Protection Factor and adequate photostability, but their toxicity is not yet known. This study aimed to evaluate the toxicity of three synthetic 2-(2'-hydroxyphenyl)benzoxazole derivatives for their possible application as sunscreens. In silico tools were used in order to assess potential risks regarding mutagenic, carcinogenic, and skin sensitizing potential. Bioassays were performed in L929 cells to assess cytotoxicity in MTT assay and genotoxic activities in the Comet assay and micronucleus test. Also, the Salmonella/microsome assay was performed to evaluate gene mutations. The in silico predictions indicate a low risk of mutagenicity and carcinogenicity of the compounds while the skin sensitizing potential was low or inconclusive. The 2-(4'-amino-2'-hydroxyphenyl)benzoxazol compound was the most cytotoxic and genotoxic among the compounds evaluated in L929 cells, but none induced mutations in the Salmonella/microsome assay. The amino substituted at the 4' position of the phenyl ring appears to have greater toxicological risks than substituents at the 5' position of 2-(phenyl)benzoxazole. The findings warrant further studies of these compounds in cosmetic formulations.

Keywords: 2-(2′-hydroxyphenyl)benzoxazole; Cytotoxicity; Genotoxicity; Mutagenicity; Sunblock; UV radiation.

MeSH terms

  • Animals
  • Benzoxazoles / chemistry
  • Benzoxazoles / toxicity*
  • Carcinogenesis / drug effects
  • Cell Line
  • Comet Assay
  • DNA Damage / drug effects
  • Mice
  • Micronucleus Tests
  • Mutagenicity Tests
  • Quantitative Structure-Activity Relationship*
  • Salmonella typhimurium / drug effects
  • Sunscreening Agents / chemistry
  • Sunscreening Agents / toxicity*

Substances

  • Benzoxazoles
  • Sunscreening Agents