1. Academic Validation
  2. Cytotoxic triterpenoid-safirinium conjugates target the endoplasmic reticulum

Cytotoxic triterpenoid-safirinium conjugates target the endoplasmic reticulum

  • Eur J Med Chem. 2021 Jan 1:209:112920. doi: 10.1016/j.ejmech.2020.112920.
Oliver Kraft 1 Marie Kozubek 1 Sophie Hoenke 1 Immo Serbian 1 Daniel Major 1 René Csuk 2
Affiliations

Affiliations

  • 1 Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle, Saale, Germany.
  • 2 Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120, Halle, Saale, Germany. Electronic address: rene.csuk@chemie.uni-halle.de.
Abstract

Safirinium P and Q fluorescence labels were synthesized and conjugated with spacered triterpenoic acids to access hybrid structures. While the parent safirinium compounds were not cytotoxic at all, many triterpenoid safirinium P and Q conjugates showed moderate cytotoxicity. An exception, however, was safirinium P derived compound 30 holding low EC50 = 5.4 μM (for A375 cells) to EC50 = 7.5 μM (for FaDu cells) as well as EC50 = 6.6 μM for non-malignant fibroblasts NIH 3T3. Fluorescence imaging showed that the safirinium core structures cannot enter the cells (not even after a prolonged incubation time of 24 h), while the conjugates (as exemplified for 30) are accumulating in the endoplasmic reticulum but not in the mitochondria. The development of safirinium-hybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents.

Keywords

Betulinic acid; Cytotoxicity; Endoplasmic reticulum; Safirinium.

Figures