Title :

Studies on phenothiazines: New microtubule-interacting compounds with phenothiazine A-ring as potent antineoplastic agents

Author(s) :

Ghinet, Alina [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Moise, Iuliana-Monica [Auteur]
Rigo, Benoit [Auteur]
Homerin, Germain [Auteur]
Farce, Amaury [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Lille Inflammation Research International Center - U 995 [LIRIC]
Dubois, Joelle [Auteur]
Bicu, Elena [Auteur]

Journal title :

Bioorganic & medicinal chemistry

Abbreviated title :

Bioorg. Med. Chem.

Volume number :

24

Pages :

2307-2317

Publication date :

2016-05-15

ISSN :

0968-0896

English keyword(s) :

Microtubule-targeting agent
Tubulin
Phenothiazine
Anticancer agent

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

New phenothiazine derivatives 6-20 have been designed, synthesized and evaluated in vitro for their ability to inhibit tubulin polymerization and antiproliferative activity against 60 cancer cell lines, including several ...
Show more >New phenothiazine derivatives 6-20 have been designed, synthesized and evaluated in vitro for their ability to inhibit tubulin polymerization and antiproliferative activity against 60 cancer cell lines, including several multi-drug resistant (MDR) tumor cell lines. The phenothiazine unit may successfully replace the classical 3,4,5-trimethoxyphenyle A ring of parent combretastatin A-4 or phenstatin, confirming previous studies. The most promising structural modulations have been realized on the B ring, the 2'-fluoro-4'-methoxy substitution in compound 6 and the 2'-trifluoromethyl-4'-methoxy substitution in compound 7 providing the best antitubulin and antitumor activity in the current study. Compounds 6-8 and 16 exhibited more important cell growth inhibition than parent phenstatin 2 on human colon Duke's type D, colorectal adenocarcinoma COLO 205 and on human kidney adenocarcinoma A498 cell lines. 10-Methylphenothiazine derivatives 19 and 20 did not show biological activity but exerted bright fluorescence and solvatochromism effects. These molecules deserve further chemical efforts in order to provide valuable tools for biophysical studies.Show less >

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Inserm
Université de Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Therapeutic innovation targetting inflammation

Submission date :

2019-05-17T13:14:39Z