Abstract |
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.
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Authors | Alina Ghinet, Cristina-Maria Abuhaie, Philippe Gautret, Benoît Rigo, Joëlle Dubois, Amaury Farce, Dalila Belei, Elena Bîcu |
Journal | European journal of medicinal chemistry
(Eur J Med Chem)
Vol. 89
Pg. 115-27
(Jan 07 2015)
ISSN: 1768-3254 [Electronic] France |
PMID | 25462232
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Indolizines
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Topics |
- 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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