Indolizine-phenothiazine hybrids as the ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity
Author(s) :
Moise, Iuliana-Monica [Auteur]
Bicu, Elena [Auteur]
Farce, Amaury [Auteur]
Dubois, Joelle [Auteur]
Ghinet, Alina [Auteur]
Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Bicu, Elena [Auteur]
Farce, Amaury [Auteur]

Dubois, Joelle [Auteur]
Ghinet, Alina [Auteur]

Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Journal title :
Bioorganic chemistry
Abbreviated title :
Bioorg. Chem.
Volume number :
103
Pages :
104184
Publication date :
2020-08-26
ISSN :
1090-2120
Keyword(s) :
Indolizine
Dual inhibitor
Antitumor agent
Farnesyltransferase inhibitor
Phenothiazine
Hybrids
Tubulin polymerization
Dual inhibitor
Antitumor agent
Farnesyltransferase inhibitor
Phenothiazine
Hybrids
Tubulin polymerization
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
In the incessant search for innovative cancer control strategies, this study was devoted to the design, synthesis and pharmacological evaluation of dual inhibitors of farnesyltransferase and tubulin polymerization (FTI/MTIs). ...
Show more >In the incessant search for innovative cancer control strategies, this study was devoted to the design, synthesis and pharmacological evaluation of dual inhibitors of farnesyltransferase and tubulin polymerization (FTI/MTIs). A series of indolizine-phenothiazine hybrids 16 (amides) and 17 (ketones) has been obtained in a 4-step procedure. The combination of the two heterocycles provided potent tubulin polymerization inhibitors with similar efficiency as the reference phenstatin and (-)-desoxypodophyllotoxin. Ketones 17 were also able to inhibit human farnesyltransferase (FTase) in vitro. Interestingly, three molecules 17c, 17d and 17f were very effective against both considered biological targets. Next, nine indolizine-phenothiazine hybrids 16c, 16f, 17a-f and 22b were evaluated for their cell growth inhibition potential on the NCI-60 cancer cell lines panel. Ketones 17a-f were the most active and displayed promising cellular activities. Not only they arrested the cell growth of almost all tested cancer cells, but they displayed cytotoxicity potential with GI50Show less >
Show more >In the incessant search for innovative cancer control strategies, this study was devoted to the design, synthesis and pharmacological evaluation of dual inhibitors of farnesyltransferase and tubulin polymerization (FTI/MTIs). A series of indolizine-phenothiazine hybrids 16 (amides) and 17 (ketones) has been obtained in a 4-step procedure. The combination of the two heterocycles provided potent tubulin polymerization inhibitors with similar efficiency as the reference phenstatin and (-)-desoxypodophyllotoxin. Ketones 17 were also able to inhibit human farnesyltransferase (FTase) in vitro. Interestingly, three molecules 17c, 17d and 17f were very effective against both considered biological targets. Next, nine indolizine-phenothiazine hybrids 16c, 16f, 17a-f and 22b were evaluated for their cell growth inhibition potential on the NCI-60 cancer cell lines panel. Ketones 17a-f were the most active and displayed promising cellular activities. Not only they arrested the cell growth of almost all tested cancer cells, but they displayed cytotoxicity potential with GI50Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Institut Pasteur de Lille
Université de Lille
Inserm
Institut Pasteur de Lille
Université de Lille
Collections :
Submission date :
2021-07-06T12:48:11Z