Discovery of Facile Amides-functionalized Rhodanine-3-acetic Acid Derivatives As Potential Anticancer Agents by Disrupting Microtubule Dynamics

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2021 Sep 16

PMID 34525898

Citations 4

Authors

Xiang Zhou

Jiamin Liu

Jiao Meng

Yihong Fu

Zhibin Wu

Guiping Ouyang

Zhenchao Wang

Affiliations

Soon will be listed here.

Abstract

Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of ()-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)--phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities . Proliferation assays identified as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound and tubulin Arg 369, which is also the binding site for the anticancer drug Taxol. Our results suggest that ()-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)--phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.

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