Novel compounds containing polar and nonpolar substitutions on the prop-2-en-1-on linker
of the trans-indol-3-ylacrylamide scaffold were designed by modeling within the colchicine
site of tubulin and then synthesized to determine the role of such substitutions on tubulin
polymerization. We first determined the in vitro antiproliferation activities of the
compounds against cancer cell lines with a particular focus on hepatocellular carcinoma. The
results indicated that five of the compounds showed moderate antitumor activities. When
the tubulin polymerization inhibitory effect of these compounds was evaluated, compound
13 was determined to be a tubulin polymerization inhibitor. Furthermore, cell cycle analysis
for compound 13 resulted in G2/M-phase arrest in Huh7 cells. The results indicated that
polar substitutions on the indole acrylamide scaffold enhance potency against tubulin
polymerization. However, the substitution-related bioactivity shifting was not observed on
the cancer cell lines since the inhibition mechanisms of the compounds may vary.

Title

Journal of Molecular Structure

Publisher

Elsevier

Publisher Country

Netherlands

Indexing

Thomson Reuters

Impact Factor

3.196

Publication Type

Both (Printed and Online)

Volume

1254

Year

2022

Pages

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