Abstract

Plants are an important source of chemically diverse natural products that target microtubules, one of the most successful targets in cancer therapy. Colchicine, paclitaxel, and vinca alkaloids are the earliest plant-derived microtubule-targeting agents (MTAs), and paclitaxel and vinca alkaloids are currently important drugs used in the treatment of cancer. Several additional plant-derived compounds that act on microtubules with improved anticancer activity are at varying stages of development. Here, we move beyond the well-discussed paclitaxel and vinca alkaloids to present other promising plant-derived MTAs with potential for development as anticancer agents. Various biological and biochemical aspects are discussed. We hope that the review will provide guidance for further exploration and identification of more effective, novel MTAs derived from plant sources.

Highlights

  • Microtubules are the major components of the eukaryotic cytoskeleton

  • Doxorubicin-resistant mouse tumor models [27,34,50]. This improved efficacy of taccalonolides may be explained by its high degree of cellular retention compared to paclitaxel that could be potentially stemmed from their covalent interaction with tubulin [51]

  • The binding pocket contained H30 -helix, T4 and T5 loops, and the H110 helix [41], demonstrating that curcumin occupies a unique site that partly overlap with the colchicine-site on tubulin

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Summary

Introduction

Microtubules are the major components of the eukaryotic cytoskeleton They are composed of α- and β-tubulin heterodimers that interconvert between phases of rapid growth (polymerization) and shrinkage (depolymerization) [1]. The in paclitaxel and vinca important for identifying novel, more effective antimicrotubule agents. 1) that exhibited bioactivity to cytotoxic activity against cancer culture and/or in xenografts here onwards) superior(termed to paclitaxel and vinca alkaloids, or (2) cells that in culture and/or xenografts here onwards) superior to paclitaxel and vinca alkaloids, or 2) that underwent clinicalintrials are discussed.

Taccalonolides
Mechanism of Action
Tubulin Binding Sites
Structure-Activity Relationships
References:
Advantages over Paclitaxel
Persin
Persin Activity in MTA-Resistant Cells
Curcumin
Structure-Activity
Combretastatins
Mechanism of Action and the Tubulin Binding Sites
Structure–Activity Relationships
Maytansinoids
Chalcones and Quercetin
Findings
Concluding Remarks and Future Perspectives
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