Tebrophen — An Old Polyphenol Drug with Anticancer Potential †
| Autor: | Mario Matijašić, Nikolina Škrobot Vidaček, Krunoslav Nujić, Milena Ivanković, Donatella Verbanac, Višnja Stepanić, Ivica Rubelj, Dubravko Jelić, Andrea Ćukušić Kalajžić |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Models Molecular Pharmaceutical Science tebrophen anticancer high-throughput screening molecular modeling population doublings Pharmacology Analytical Chemistry HeLa 0302 clinical medicine Catalytic Domain Drug Discovery Enzyme Inhibitors Respiratory Burst 0303 health sciences education.field_of_study ZAP-70 Protein-Tyrosine Kinase biology Cell Death Kinase Free Radical Scavengers Flow Cytometry 3. Good health molecular modelling Drug development Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine Female Programmed cell death Dipeptidyl Peptidase 4 Population Polybrominated Biphenyls Antineoplastic Agents Article 03 medical and health sciences Inhibitory Concentration 50 Cell Line Tumor medicine Animals Humans Physical and Theoretical Chemistry education IC50 030304 developmental biology Cell Proliferation Organic Chemistry Infant Newborn Cancer Polyphenols Basic Medical Sciences Fibroblasts biology.organism_classification medicine.disease Cell culture Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Drug Screening Assays Antitumor Phytotherapy |
| Zdroj: | Molecules Volume 17 Issue 7 Pages 7864-7886 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules17077864 |
| Popis: | In vitro high-throughput screening was carried out in order to detect new activities for old drugs and to select compounds for the drug development process comprising new indications. Tebrophen, a known antiviral drug, was found to inhibit activities on inflammation and cancer related targets. In primary screening this semisynthetic halogenated polyphenol was identified to inhibit the activities of kinases ZAP-70 and Lck (IC50 0.34 μM and 16 μM, respectively), as well as hydrolase DPPIV (at 80 μM 41% inhibition). Next, it showed no cytotoxic effects on standard cell lines within 24 h. However, tebrophen slowed propagation of breast cancer (MDA-MB-231), osteosarcoma (U2OS) and cervical carcinoma (HeLa), through at least 35 population doublings in a dose-dependent manner. It completely stopped the division of the prostate cancer (PC3) cell line at 50 μM concentration and the cells entered massive cell death in less than 20 days. On the other hand, tebrophen did not influence the growth of normal fibroblasts. According to the measured oxidative burst and estimated in silico parameters its direct antioxidative ability is limited. The obtained results indicate that tebrophen can be considered a promising lead molecule for generating more soluble derivatives with specific anticancer efficacy. |
| Databáze: | OpenAIRE |
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