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
Posted ContentDOI
Lead optimization of novel quinolone chalcone compounds by a structure-activity relationship (SAR) study to increase efficacy and metabolic stability.
James Knockleby,Aïcha Dede Djigo,Indeewari Kalhari Lindamulage,C. Karthikeyan,Piyush Trivedi,Hoyun Lee +5 more
TL;DR: In this article, the authors synthesized 17 quinolone-chalcone derivatives based on CTR-17 and CTR-20, and carried out a structure-activity relationship study.
Journal ArticleDOI
Synthesis, molecular docking, and saturation-transfer difference NMR spectroscopy of longipinane derivatives as novel microtubule stabilizers
Esmeralda J. Chávez-Estrada,Carlos M. Cerda-García-Rojas,Luisa U. Román-Marín,Juan D. Hernández-Hernández,Pedro Joseph-Nathan +4 more
TL;DR: Molecular docking studies revealed that 5 interacts at the paclitaxel binding site of tubulin, suggesting that this could be the mechanism for producing microtubule stability, while saturation-transfer difference NMR spectroscopy experimentally confirmed that 5 binds to tubulin.
Journal ArticleDOI
Synthesis, Antiproliferative Activity, and Effect on Carcinoma A549 Cell Microtubules of New Tubuloclustin Analogs
N. A. Zefirov,N. A. Zefirov,Yu. A. Evteeva,A. R. Fatkulin,S. Schulz,S. A. Kuznetsov,Olga N. Zefirova,Olga N. Zefirova +7 more
TL;DR: Tests in vivo of N-[6-(adamantyl)-6-oxoheaxnoyl]-N-deacetylcolchicine on carcinoma A549 experimental models were concluded to be promising and all compounds induced apoptosis of A549 cells.
Journal ArticleDOI
Reversible Photocontrol of Microtubule Stability by Spiropyran‐Conjugated Tau‐Derived Peptides
Hiroshi Inaba,Minamo Sakaguchi,Soei Watari,Shigesaburo Ogawa,Arif Md. Rashedul Kabir,Akira Kakugo,Kazuki Sada,Kazunori Matsuura +7 more
TL;DR: In this article , a Tau-derived peptide was conjugated to spiropyran, which is reversibly converted to merocyanine by light, as a reversible photocontrol system to stabilize microtubules.
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