Synthesis, DNA/RNA-interaction and biological activity of benzo[k,l]xanthene lignans
| Autor: | Kristina Žuna, Nunzio Cardullo, Luana Pulvirenti, Corrado Tringali, Ivo Crnolatac, Marijana Jukić, Marijana Radić Stojković, Ljubica Glavaš-Obrovac, Vera Muccilli, Lidija-Marija Tumir, Iva Zonjić, Sandra Radić Brkanac, Ksenija Durgo, Ana Huđek |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Staphylococcus aureus
Circular dichroism Stereochemistry Intercalation (chemistry) Antineoplastic Agents Serum Albumin Human Ring (chemistry) 01 natural sciences Biochemistry Lignans Circulating Tumor DNA Structure-Activity Relationship chemistry.chemical_compound DNA/RNA recognition Benzo[k l]xanthene lignans G-quadruplex interaction HSA interaction Antiproliferative effect Drug Discovery Tumor Cells Cultured Humans RNA Neoplasm Biology Molecular Biology Cell Proliferation Xanthene Dose-Response Relationship Drug Escherichia coli K12 Molecular Structure Analytic Chemistry 010405 organic chemistry Organic Chemistry Salmonella enterica RNA Biological activity 3. Good health 0104 chemical sciences 010404 medicinal & biomolecular chemistry Xanthenes chemistry Drug Screening Assays Antitumor Derivative (chemistry) DNA |
| Zdroj: | Bioorganic chemistry |
| Popis: | Interactions of two newly synthesized and six previously reported benzoxanthene lignans (BXLs), analogues of rare natural products, with DNA/RNA, G-quadruplex and HSA were evaluated by a set of spectrophotometric methods. Presence/absence of methoxy and hydroxy groups on the benzoxanthene core and minor modifications at C-1/C-2 side pendants – presence/absence of phenyl ring and presence/absence of methoxy and hydroxy groups on phenyl ring – influenced the fluorescence changes and the binding strength to double- stranded (ds-) and G-quadruplex structures. In general, compounds without phenyl ring showed stronger fluorescence changes upon binding than phenyl-substituted BXLs. On the other hand, BXLs with an unsubstituted phenyl ring showed the best stabilization effects of G-quadruplex. Circular dichroism spectroscopy results suggest mixed binding mode, groove binding and partial intercalation, to ds-DNA/RNA and end- stacking to top or bottom G-tetrads as the main binding modes of BXLs to those targets. All compounds exhibited micromolar binding affinities toward HSA and an increased protein thermal stability. Moderate to strong antiradical scavenging activity was observed for all BXLs with hydroxy groups at C-6, C-9 and C-10 positions of the benzoxanthene core, except for derivative bearing methoxy groups at these positions. BXLs with unsubstituted or low-substituted phenyl ring and one derivative without phenyl ring showed strong growth inhibition of Gram- positive Staphylococcus aureus. All compounds showed moderate to strong tumor cell growth- inhibitory activity and cytotoxicity. |
| Databáze: | OpenAIRE |
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