US EPA

1600115 

Journal Article 

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

Racané, L; Pavelić, SK; Nhili, R; Depauw, S; Paul-Constant, C; Ratkaj, I; David-Cordonnier, MH; Pavelić, K; Tralić-Kulenović, V; Karminski-Zamola, G 

2013 

Yes 

European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 

63 

882-891 

English 

23603616 

10.1016/j.ejmech.2013.02.026 

WOS:000322855400086 

https://linkinghub.elsevier.com/retrieve/pii/S0223523413001335
Exit
 

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. 

Amdino-substituted phenylene-bisbenzothiazoles; Antitumour evaluation; DNA-binding; Apoptosis