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Review
. 2023 Mar 23;24(7):6063.
doi: 10.3390/ijms24076063.

Epothilones as Natural Compounds for Novel Anticancer Drugs Development

Cecilia Villegas  1 , Iván González-Chavarría  2 , Viviana Burgos  3   4 , Héctor Iturra-Beiza  3 , Henning Ulrich  5 , Cristian Paz  1
Affiliations
Review

Epothilones as Natural Compounds for Novel Anticancer Drugs Development

Cecilia Villegas et al. Int J Mol Sci. .

Abstract

Epothilone is a natural 16-membered macrolide cytotoxic compound produced by the metabolism of the cellulose-degrading myxobacterium Sorangium cellulosum. This review summarizes results in the study of epothilones against cancer with preclinical results and clinical studies from 2010-2022. Epothilone have mechanisms of action similar to paclitaxel by inducing tubulin polymerization and apoptosis with low susceptibility to tumor resistance mechanisms. It is active against refractory tumors, being superior to paclitaxel in many respects. Since the discovery of epothilones, several derivatives have been synthesized, and most of them have failed in Phases II and III in clinical trials; however, ixabepilone and utidelone are currently used in clinical practice. There is robust evidence that triple-negative breast cancer (TNBC) treatment improves using ixabepilone plus capecitabine or utidelone in combination with capecitabine. In recent years innovative synthetic strategies resulted in the synthesis of new epothilone derivatives with improved activity against refractory tumors with better activities when compared to ixabepilone or taxol. These compounds together with specific delivery mechanisms could be developed in anti-cancer drugs.

Keywords: anticancer agents; clinical trials; cytotoxicity; epothilone derivates; epothilones; refractory cancer; taxanes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical Structure of the natural Epothilone A and the taxane Paclitaxel.
Figure 2
Figure 2
Structure of natural and synthetic epothilone with anticancer activity clinically evaluated. In red are remarked the main differences with EpoB.
Figure 3
Figure 3
Subdivision of the EpoB structure into four regions (A–D) based on structure activity relationship [9,25].
Figure 4
Figure 4
Mechanisms of action of epothilones. (left) Evasion of MDR-associated resistance. (centre) Stabilization of microtubules and inhibition of mitosis. (right) Induction of apoptosis.
Figure 5
Figure 5
Chemical structures of the most active epothilone derivatives. These structures were published by [123]. Cytotoxic activities are reported in Table 4.
Figure 6
Figure 6
Structure of selected 12, 13-Aziridinyl epothilones with cytotoxic activity.
See this image and copyright information in PMC

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