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

Hawash M., KAHRAMAN D. C., OLĞAÇ A., Ergun S. G., Hamel E., Cetin-Atalay R., ...More

Journal of Molecular Structure, vol.1254, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1254
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2022.132345
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • 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
  • Gazi University Affiliated: Yes


© 2022Novel 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.