Studies on indolizines. Evaluation of their biological properties as microtubule-interacting agents and as melanoma targeting compounds.

With the aim of investigating new analogues of phenstatin with an indolizin-3-yl unit, in particular as the B-ring, three new series of compounds (6-8, 9-34 and 54) were synthesized and tested for interactions with tubulin polymerization and evaluated for cytotoxicity on an NCI-60 human cancer cell lines panel. The replacement of the 3'-hydroxy-4'-methoxyphenyl B-ring of phenstatin with substituted indolizine unit results in the conservation of both antitubulin and cytotoxic effect. Indolizines 9 and 17 were the most effective in the present study and showed the highest antiproliferative effect on melanoma cell lines MDA-MB-435 (GI50 = 30 nM) and could serve as new lead compounds for the development of anti-cancer therapeutics.
AuthorsAlina Ghinet, Cristina-Maria Abuhaie, Philippe Gautret, Benoît Rigo, Joëlle Dubois, Amaury Farce, Dalila Belei, Elena Bîcu
JournalEuropean journal of medicinal chemistry (Eur J Med Chem) Vol. 89 Pg. 115-27 (Jan 7 2015) ISSN: 1768-3254 [Electronic] France
PMID25462232 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Masson SAS. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Indolizines
  • Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Indolizines (chemical synthesis, chemistry, pharmacology)
  • Melanoma (drug therapy, pathology)
  • Microtubules (drug effects)
  • Molecular Structure
  • Structure-Activity Relationship

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