Potential cytotoxic and selective effect of new benzo[b]xanthenes against oral squamous cell carcinoma

Future Med Chem. 2018 May 1;10(10):1141-1157. doi: 10.4155/fmc-2017-0205. Epub 2018 May 11.

Abstract

Aim: The current work shows a new synthetic methodology to obtain 21 naphthoquinones that have been evaluated against oral cavity cancer. The compounds were obtained by a three-component reaction involving lawsone, dimedone and aromatic aldehydes catalyzed by lithium chloride under microwave irradiation to produce families of 1,4- and 1,2-naphthoquinones.

Results: A clonogenic assay was performed on SCC9 cell line cultures with all compounds, revealing five very active compounds. In the 3,4,5-dimethylthiazol-2,5-diphenyltetrazolium bromide cell viability assay using three different cell lines (SCC9, SCC4 and SCC25), 8c had an average IC50 of approximately 1.45 μM capable of reducing tumor cell viability, approximately 90-times higher than carboplatin.

Conclusion: Therefore, the xanthene-naphthoquinone derivatives show promising bioactivity for oral cavity cancer treatment.

Keywords: Knoevenagel condensation; clonogenic assay; cytotoxicity; hemolytic activity; lapachones; lawsone; multicomponent reactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carboplatin / pharmacology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Erythrocytes / cytology
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Hemolysis / drug effects
  • Humans
  • Mice
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology
  • NIH 3T3 Cells
  • Naphthoquinones / chemistry
  • Structure-Activity Relationship
  • Xanthenes / chemical synthesis
  • Xanthenes / chemistry*
  • Xanthenes / pharmacology

Substances

  • Antineoplastic Agents
  • Naphthoquinones
  • Xanthenes
  • Carboplatin