Transformation of asiatic acid into a mitocanic, bimodal-acting rhodamine B conjugate of nanomolar cytotoxicity

Eur J Med Chem. 2018 Nov 5:159:143-148. doi: 10.1016/j.ejmech.2018.09.066. Epub 2018 Sep 26.

Abstract

Based on their biological activity natural products continue to represent optimal lead structures for the development of novel drug candidates. We focused on the syntheses of several derivatives of the triterpene asiatic acid and on the evaluation of their cytotoxic activity in a photometric sulforhodamin B assay. Especially, benzamide 2 and rhodamine B conjugate 11 show a distinct cytotoxicity for several human tumor cell lines, e.g. EC50 (A2780) = 110 ± 1 nM and EC50 (A2780) = 8 ± 2 nM, respectively. Interestingly, compound 11 showed for two human tumor cell lines (HT29 and 518A2) non-linear, bimodal dose-response relationships.

Keywords: Asiatic acid; Bimodal; Cytotoxicity; Mitocan; Rhodamine B; Triterpene.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / chemical synthesis
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Molecular Structure
  • NIH 3T3 Cells
  • Pentacyclic Triterpenes / chemical synthesis
  • Pentacyclic Triterpenes / chemistry
  • Pentacyclic Triterpenes / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Pentacyclic Triterpenes
  • asiatic acid