Novel substituted aminothiazoles as potent and selective anti-hepatocellular carcinoma agents
| Autor: | Shigeki Nakagawa, John Rogowskyj, Xiaodong Xu, William A. Kinney, Nicolas Goossens, Takaaki Higashi, Anu Venkatesh, Yujin Hoshida, Timothy M. Block, Huagang Lu, Spiros P. Hiotis, Myron E. Schwarz, Anna P. Koh, Yanming Du, Noshena Khan, Ganesh Gunasekaran, Andrea Cuconati, Wenquan Yu |
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| Jazyk: | angličtina |
| Předmět: |
Carcinoma
Hepatocellular Stereochemistry Clinical Biochemistry Carbonates Pharmaceutical Science Antineoplastic Agents Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Aminothiazole Cell Line Tumor Drug Discovery medicine Humans Prodrugs Molecular Biology Amination Cell Proliferation Chemistry Liver Neoplasms Organic Chemistry Prodrug medicine.disease 3. Good health Thiazoles Liver Cell culture 030220 oncology & carcinogenesis Hepatocellular carcinoma Toxicity Molecular Medicine 030211 gastroenterology & hepatology Liver cancer Selectivity Isopropyl |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2016.10.015 |
| Popis: | Based on our previous identification of a disubstituted aminothiazole termed HBF-0079 with promising selective toxicity for HCC-derived cell lines versus non-HCC liver lines, a series of tri-substituted aminothiazole derivatives were prepared and evaluated. This work resulted in the discovery of isopropyl 4-(pyrazin-2-yl)-2-(pyrimidin-2-ylamino)thiazole-5-carboxylate, 14, which displayed EC50 value of 0.11μM and more than 450times of selectivity, and its methyl carbonate prodrug 24 with improved solubility in organic solvents. Furthermore, 14, was shown to reduce the proliferation of several liver cancer cells derived directly from patients. |
| Databáze: | OpenAIRE |
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