4.7 Article

Semi-synthesis and antiproliferative evaluation of PEGylated pentacyclic triterpenes

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 118, Issue -, Pages 64-78

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2016.04.016

Keywords

Triterpene; Oleanolic acid; Maslinic acid; PEGylation; Apoptosis

Funding

  1. Consejeria de Innovacion, Ciencia y Empresa of the Junta de Andalucia [FQM-7372]
  2. Plan Propio of the University of Granada

Ask authors/readers for more resources

Several PEGylated derivatives of oleanolic and maslinic acids have been semi-synthesized, attaching one acid-PEG reagent to the hydroxyl groups at C-2 or C-2/C-3 of the A rings of these natural triterpenes, and also to their corresponding C-28 benzyl derivatives. Several monomeric and dimeric PEGylated compounds have also been produced by linking one diamine-PEG reagent to the carboxyl group at C-28 of the same natural triterpenes and also to their corresponding C-2 or C-2/C-3 acetylated derivatives. The cytotoxic effects of 12 triterpenic PEGylated derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed. The best results have been achieved by the PEGylated-amine derivative of oleanolic acid, with IC50 concentrations between 0.22 and 3.78 mu M, being between 28- and 963-fold more effective than its natural precursor. The percentages of apoptosis induction have also been determined for the five PEGylated derivatives with the lowest cytotoxicity data. All five compounds showed apoptotic effects on the treated cells, with a total apoptosis rate of 99% in the B16-F10 cells, 80% in the Hep G2 cells, and 51% in the HT29 cells. We have also studied the changes in the mitochondrial membrane potential (MMP) to elucidate the possible mechanism involved in the apoptotic responses (intrinsic or extrinsic). Finally, to verify the results found in the cytometry assays, we have used fluorescence microscopy techniques to determine changes in the cell morphology. These PEGylated derivatives of natural triterpenoids, which can induce apoptosis at very low concentrations in different tumour lines, may represent new effective therapeutic drugs against these diseases. (C) 2016 Elsevier Masson SAS. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available