Inhibitory Effect of New Semisynthetic Usnic Acid Derivatives on Human Tyrosyl-DNA Phosphodiesterase 1
| Autor: | Nariman F. Salakhutdinov, D. K. Nilov, Alexandra L. Zakharenko, Olga I. Lavrik, Olga A. Luzina, Maxim Kuprushkin, Aleksandr Filimonov, I. V. Gushchina, Ekaterina S Ilina, Olga D. Zakharova, Vytas K. Švedas, Nadezhda S Dyrkheeva |
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| Rok vydání: | 2018 |
| Předmět: |
Phosphodiesterase Inhibitors
Pharmaceutical Science Context (language use) 01 natural sciences Analytical Chemistry chemistry.chemical_compound Cell Line Tumor Drug Discovery Escherichia coli Moiety Humans MTT assay Benzofurans Pharmacology biology 010405 organic chemistry Phosphoric Diester Hydrolases Topoisomerase Organic Chemistry Usnic acid Phosphodiesterase Biological activity Tyrosyl-DNA Phosphodiesterase 1 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry HEK293 Cells Complementary and alternative medicine chemistry Biochemistry biology.protein MCF-7 Cells Molecular Medicine Microorganisms Genetically-Modified |
| Zdroj: | Planta medica. 85(2) |
| ISSN: | 1439-0221 |
| Popis: | Usnic acid, a lichen secondary metabolite produced by a whole number of lichens, has attracted the interest of researchers owing to its broad range of biological activity, including antiviral, antibiotic, anticancer properties, and it possessing a certain toxicity. The synthesis of new usnic acid derivatives and the investigation of their biological activity may lead to the discovery of compounds with better pharmacological and toxicity profiles. In this context, a series of new usnic acid derivatives comprising a terpenoid moiety were synthesized, and their ability to inhibit the catalytic activity of the human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 was investigated. The most potent compounds (15a, 15b, 15g, and 16a, 16b, 16g) had IC50 values in the range of 0.33 – 2.7 µM. The inhibitory properties were mainly dependent on the flexibility and length of the terpenoid moiety, but not strongly dependent on the configuration of the asymmetric centers. The synthesized derivatives showed low cytotoxicity against human cell lines in an MTT assay. They could be used as a basis for the development of more effective anticancer therapies when combined with topoisomerase 1 inhibitors. |
| Databáze: | OpenAIRE |
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