Arrhythmias and antiarrhythmic drugs: Mechanism of action and structure–activity relationships II11Editor's note: Part I of this article appeared in the April 1976 issue of the Journal of Pharmaceutical Sciences.

1976 ◽  
Vol 65 (5) ◽  
pp. 635-648 ◽  
Author(s):  
P.H. Morgan ◽  
I.W. Mathison
Keyword(s):  
Mechanism Of Action ◽  
Antiarrhythmic Drugs ◽  
Pharmaceutical Sciences ◽  
Structure Activity Relationships ◽  
Structure Activity

Structure–activity relationships of 4-N-substituted ferroquine analogues: Time to re-evaluate the mechanism of action of ferroquine

2009 ◽  
Vol 694 (6) ◽  
pp. 845-854 ◽  
Author(s):  
Christophe Biot ◽  
Natascha Chavain ◽  
Faustine Dubar ◽  
Bruno Pradines ◽  
Xavier Trivelli ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Structure Activity Relationships ◽  
Structure Activity

scholarly journals Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 920
Author(s):  
Xiaoyan Chen ◽  
Angela Winstead ◽  
Hongtao Yu ◽  
Jiangnan Peng
Keyword(s):  
Drug Resistance ◽  
Mechanism Of Action ◽  
Covalent Binding ◽  
Chemotherapeutic Agents ◽  
Stabilizing Agents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Unique Mechanism

Microtubule stabilizing agents, such as paclitaxel, docetaxel, and cabazitaxel have been among the most used chemotherapeutic agents in the last decades for the treatment of a wide range of cancers in the clinic. One of the concerns that limit their use in clinical practice is their intrinsic and acquired drug resistance, which is common to most anti-cancer chemotherapeutics. Taccalonolides are a new class of microtubule stabilizers isolated from the roots of a few species in the genus of Tacca. In early studies, taccalonolides demonstrated different effects on interphase and mitotic microtubules from those of paclitaxel and laulimalide suggesting a unique mechanism of action. This prompts the exploration of new taccalonolides with various functionalities through the identification of minor constituents of natural origin and semi-synthesis. The experiments on the new highly potent taccalonolides indicated that taccalonolides possessed a unique mechanism of covalently binding to the microtubule. An X-ray diffraction analysis of a crystal of taccalonolides AJ binding to tubulin indicated that the covalent binding site is at β-tubulin D226. Taccalonolides circumvent all three mechanisms of taxane drug resistance both in vitro and in vivo. To improve the activity, the structure modification through semi-synthesis was conducted and the structure-activity relationships (SARs) was analyzed based on natural and semi-synthetical taccalonolides. The C22–C23 epoxide can significantly increase the antiproliferation potency of taccalonolides due to the covalent link of C22 and the carboxylic group of D226. Great progress has been seen in the last few years in the understanding of the mechanism of this class of microtube-stabilizing agents. This review summarizes the structure diversity, structure-activity relationships (SARs), mechanism of action, and in vivo activities of taccalonolides.

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