A Multitarget Approach toward the Development of 8-Substituted Purines for Photoprotection and Prevention of UV-Related Damage

ChemMedChem. 2017 May 22;12(10):760-769. doi: 10.1002/cmdc.201700137. Epub 2017 May 3.

Abstract

Ultraviolet (UV) light is the most abundant and significant modifiable risk factor for skin cancer and many other skin diseases such as early photo-aging. Across the solar radiation spectrum, UV light is the main cause behind skin problems. In the search for novel photoprotective compounds, a new series of 8-substituted purines were synthesized from commercially available 6-hydroxy-4,5-diaminopyrimidine hemisulfate or 4,5-diaminopyrimidine. All title compounds were investigated for their UV filtering, antioxidant, antifungal, and antiproliferative activities. For the photoprotection assays we used a diffuse transmittance technique to determine the sun protection factor (SPF) in vitro, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) tests for evaluating the antioxidant activity of the more potent compounds. Among them, 8-(2,5-dihydroxyphenyl)-7H-purin-6-ol (compound 26) proved to be a good radical scavenger and is also endowed with broad-spectrum UVA filtering capabilities, suitable for further development as a protective molecule.

Keywords: UV filtering; antioxidants; benzimidazoles; polyphenols; purines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fungi / drug effects
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Purines / chemical synthesis
  • Purines / chemistry*
  • Purines / pharmacology*
  • Radiation-Protective Agents / chemical synthesis
  • Radiation-Protective Agents / chemistry
  • Radiation-Protective Agents / pharmacology*
  • Structure-Activity Relationship
  • Sun Protection Factor
  • Ultraviolet Rays / adverse effects*

Substances

  • Antifungal Agents
  • Antineoplastic Agents
  • Antioxidants
  • Purines
  • Radiation-Protective Agents