Synthesis, and biological evaluation of 2-(4-aminophenyl)benzothiazole derivatives as photosensitizing agents

Bioorg Med Chem. 2010 Aug 15;18(16):6197-207. doi: 10.1016/j.bmc.2010.04.082. Epub 2010 Apr 29.

Abstract

Photodynamic therapy (PDT) employing exogenous photosensitizers is currently being approved for treatment of basal cell carcinoma (BCC). 2-(4-Aminophenyl)benzothiazoles (6) consist of chromophoric structure and absorb light in the UVA (315-400 nm). These results encouraged us to design and synthesize a diversity of 2-phenylbenzothiazoles (6). Studies on the apoptotic mechanism involved in photosensitive effects induced by UVA-activated 6 in BCC cells are carried out in the present article. 6-UVA-treated cells displayed several features of apoptosis, including an increase in the sub-G1 population, a significantly increased annexin V binding, and activation of caspase-3. 6-UVA induced a decrease in mitochondrial membrane potential (Deltapsi(mt)) and ATP via enhanced ROS generation and promoted phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK expression. These results suggest that 6-UVA elicits photosensitive effects in mitochondria processes which involve ERK and p38 activation, and ultimately lead to BCC cell apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Benzothiazoles / chemical synthesis
  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacology*
  • Carcinoma, Basal Cell / drug therapy*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Mitochondria / radiation effects
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology*
  • Ultraviolet Rays

Substances

  • 2-(4-aminophenyl)benzothiazole
  • Benzothiazoles
  • Photosensitizing Agents