Drugs that target dynamic microtubules: a new molecular perspective.
Reads0
Chats0
TLDR
The effects of microtubule‐binding chemotherapeutic agents are reviewed from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of micro Tubule assembly or disassembly.Abstract:
Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.read more
Citations
More filters
Journal ArticleDOI
Molecular simulations of drug–receptor complexes in anticancer research
TL;DR: This review provides an overall perspective of the main methods and focuses on some selected applications to both classical and novel anticancer targets.
Journal ArticleDOI
Synthesis and Biological Activity of Ferrocenyl and Ruthenocenyl Analogues of Etoposide: Discovery of a Novel Dual Inhibitor of Topoisomerase II Activity and Tubulin Polymerization.
Karolina Chrabąszcz,Andrzej Błauż,Martyna Gruchała,Marcin Wachulec,Błażej Rychlik,Damian Plażuk +5 more
TL;DR: Two series of the ferrocenyl and ruthenocenyl analogues of etoposide bearing 1,2,3-triazolyl or aminoalkyl linker were synthesized and evaluated for their cytotoxic properties, influence on the cell cycle, ability to induce tubulin polymerization, and inhibition of topoisomerase II activity.
Journal ArticleDOI
Design, Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block.
Walter D. Guerra,Daniel Lucena-Agell,Rafael Hortigüela,Roberto A. Rossi,J. Fernando Díaz,José M. Padrón,Silvia M. Barolo +6 more
TL;DR: In this article, a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides were presented.
Journal ArticleDOI
CKT0353, a novel microtubule targeting agent, overcomes paclitaxel induced resistance in cancer cells
Jelena Dinić,Carla Ríos-Luci,Ieva Karpaviciene,Inga Cikotiene,Miguel X. Fernandes,Milica Pešić,José M. Padrón +6 more
TL;DR: The ability of CKT0353 to overcome this classic MDR mechanism involved in resistance to various MTAs is demonstrated, suggesting that C KT0353 is an excellent candidate for further optimization as a therapeutic agent against tumors with MDR phenotype.
Journal ArticleDOI
Design, synthesis and biological evaluation of a series of new resveratrol analogues as potential anti-cancer agents.
TL;DR: Cell apoptosis and cell cycle assays demonstrated that compound r significantly induced apoptosis (p < 0.001) and arrested cell cycle at S phase and docking simulations supported the pharmacological results of compound r.
References
More filters
Journal ArticleDOI
Microtubules as a target for anticancer drugs.
Mary Ann Jordan,Leslie Wilson +1 more
TL;DR: Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy, and it is now known that at lower concentrations, microtubule-targeted drugs can suppress micro Tubule dynamics without changingmicrotubule mass; this action leads to mitotic block and apoptosis.
Journal ArticleDOI
Dynamic instability of microtubule growth
TL;DR: It is reported here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently and this dynamic instability is a general property of micro Tubules and may be fundamental in explaining cellular microtubule organization.
Journal ArticleDOI
Microtubule polymerization dynamics
TL;DR: This review describes progress toward understanding the mechanism of dynamic instability of pure tubulin and discusses the function and regulation of microtubule dynamic instability in living cells.
Journal ArticleDOI
Kinesin and Dynein Superfamily Proteins and the Mechanism of Organelle Transport
TL;DR: This review focuses on the molecular mechanism of organelle transport in cells and describes kinesin and dynein superfamily proteins.
Journal ArticleDOI
Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain
Raimond B. G. Ravelli,Benoît Gigant,Patrick A. Curmi,Isabelle Jourdain,Sylvie Lachkar,André Sobel,Marcel Knossow +6 more
TL;DR: Changes in the subunits of tubulin as it switches from its straight conformation to a curved one correlate with the loss of lateral contacts and provide a rationale for the rapid microtubule depolymerization characteristic of dynamic instability.
Related Papers (5)
Microtubule-binding agents: a dynamic field of cancer therapeutics
Charles Dumontet,Mary Ann Jordan +1 more