Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents

Date

2022-04-01

Author

Hawash, Mohammed
Kahraman, Deniz Cansen
OLĞAÇ, ABDURRAHMAN
Ergun, Sezen Guntekin
Hamel, Ernest
Cetin-Atalay, Rengul
BAYTAŞ, SULTAN

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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.

Subject Keywords

Synthesis, Anticancer activity, Indole, Tubulin polymerization, Colchicine binding, Cell cycle arrest, Molecular docking, BIOLOGICAL EVALUATION, ACCURATE DOCKING, POLYMERIZATION, INHIBITORS, BINDING, MICROTUBULES, EXPRESSION, PHOSPHATE, ANALOGS, GROWTH

URI

https://hdl.handle.net/11511/96043

Journal

JOURNAL OF MOLECULAR STRUCTURE

DOI

https://doi.org/10.1016/j.molstruc.2022.132345

Collections

Graduate School of Informatics, Article

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Citation Formats

M. Hawash et al., “Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents,” JOURNAL OF MOLECULAR STRUCTURE, vol. 1254, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/96043.