New anticancer active and selective phenylene-bisbenzothiazoles: Synthesis, antiproliferative evaluation and DNA binding
| Autor: | Sandra Kraljević Pavelić, Charles Paul-Constant, Sabine Depauw, Raja Nhili, Grace Karminski-Zamola, Marie-Hélène David-Cordonnier, Krešimir Pavelić, Livio Racane, Ivana Ratkaj, Vesna Tralić-Kulenović |
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| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
Antineoplastic Agents Apoptosis amdino-substituted phenylene-bisbenzothiazoles antitumor evaluation DNA-binding apoptosis Nucleic Acid Denaturation Cell Line Structure-Activity Relationship chemistry.chemical_compound Acetic acid Phenylene Cell Line Tumor Drug Discovery Humans Benzothiazoles Cytotoxicity Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure biology Circular Dichroism Topoisomerase Cell Cycle Organic Chemistry Free base DNA General Medicine Condensation reaction Combinatorial chemistry Phthalic acid Models Chemical chemistry Spectrophotometry MCF-7 Cells biology.protein Selectivity HeLa Cells |
| Zdroj: | European Journal of Medicinal Chemistry. 63:882-891 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2013.02.026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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