Title :

New anticancer active and selective phenylene-bisbenzothiazoles: Synthesis, antiproliferative evaluation and DNA binding

Author(s) :

Racané, Livio [Auteur]
Pavelić, Sandra Kraljević [Auteur]
Nhili, Raja [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Depauw, Sabine [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Ratkaj, Ivana [Auteur]
David-Cordonnier, Marie-Hélène [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]
Pavelić, Krešimir [Auteur]
Tralić-Kulenović, Vesna [Auteur]
Karminski-Zamola, Grace [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837 [JPArc]

Journal title :

European Journal of Medicinal Chemistry

Abbreviated title :

European Journal of Medicinal Chemistry

Volume number :

63

Pages :

p.882-891

Publisher :

Elsevier BV

Publication date :

2013-05

ISSN :

0223-5234

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their antiproliferative activity against several human cancer cell lines, as well as DNA-binding properties. The synthetic approach ...
Show more >Novel amidino-derivatives of phenylene-bisbenzothiazoles were synthesized and tested for their antiproliferative activity against several human cancer cell lines, as well as DNA-binding properties. The synthetic approach used for preparation of isomeric amidino substituted-phenylene-bis-benzothyazoles 3a-3f was achieved by condensation reaction of isophthaloyl dichloride 1a and terephthaloyl dichloride 1b or with phthalic acid 1c with 5-amidinium-2-aminobenzothiolate 2a and 5-(imidazolinium-2-yl)-2-aminobenzothiolate 2b in good yields. The targeted compounds were converted in the desired water soluble dihydrochloride salts by reaction of appropriate free base with concd HCl in ethanol or acetic acid. All tested compounds (3a-3f) showed antiproliferative effects on tumour cells in a concentration-dependant manner. The strongest activity and cytotoxicity was observed for diimidazolinyl substituted phenylene-bisbenzothiazole compound 3b. These effects were shown to be related to DNA-binding properties, topoisomerase I and II poisoning effects and apoptosis induction. The highest tested selectivity towards tumour cells was observed for the imidazolyl substituted phenylene-benzothiazole 3d that showed no cytotoxic effects on normal fibroblasts making it an excellent candidate for further chemical optimization and preclinical evaluation.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Autres travaux scientifiques

Submission date :

2024-07-16T15:21:39Z
2024-08-30T07:25:24Z