Issue 10, 2017

Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity

Abstract

A series of new betulinic and ursolic acid conjugates with a lipophilic triphenylphosphonium cation, meant to enhance the bioavailability and mitochondriotropic action of natural triterpenes, have been synthesized. The in vitro experiments on three human cancer cell lines (MCF-7, HCT-116 and TET21N) revealed that all the obtained triphenylphosphonium triterpene acid derivatives not only showed higher cytotoxicity as compared to betulinic acid but were also markedly superior in triggering mitochondria-dependent apoptosis, as assessed using a range of apoptosis markers such as cytochrome c release, stimulation of caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase, which is one of the targets of caspase 3. The IC50 was much lower for all triphenylphosphonium derivatives when compared to betulinic acid. Out of the tested group of conjugates, the most potent toxicity was exhibited by the betulinic acid conjugate 9 (for 9, the IC50 values against MCF-7 and TET21N cells were 0.70 μM and 0.74 μM; for betulinic acid (BA), IC50 > 25 μM against MCF-7 cells).

Graphical abstract: Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity

Supplementary files

Article information

Article type
Research Article
Submitted
15 May 2017
Accepted
17 Aug 2017
First published
13 Sep 2017
This article is Open Access
Creative Commons BY-NC license

Med. Chem. Commun., 2017,8, 1934-1945

Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and anticancer activity

D. A. Nedopekina, R. R. Gubaidullin, V. N. Odinokov, P. V. Maximchik, B. Zhivotovsky, Y. P. Bel'skii, V. A. Khazanov, A. V. Manuylova, V. Gogvadze and A. Yu. Spivak, Med. Chem. Commun., 2017, 8, 1934 DOI: 10.1039/C7MD00248C

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