Cytotoxic triterpenoid-safirinium conjugates target the endoplasmic reticulum

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 mu M (for A375 cells) to EC50 = 7.5 mu M (for FaDu cells) as well as EC50 = 6.6 mu M 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 safiriniumehybrids targeting the endoplasmic reticulum can be regarded as a promising strategy in the development of cytotoxic agents. (C) 2020 Elsevier Masson SAS. All rights reserved.

Automated summary

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, with one compound demonstrating low cytotoxicity in both malignant and non-malignant cells, indicating potential therapeutic activity.