Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation
| Autor: | Marta Ferraroni, Riccardo Rigo, Carla Bazzicalupi, Paola Gratteri, Francesco Papi, Claudia Sissi, S. Da Ros |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Coptisine Berberine Molecular model Stereochemistry Berberine Alkaloids Pharmaceutical Science Crystallography X-Ray Ligands G-quadruplex Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Alkaloids 0302 clinical medicine Drug Discovery Humans Moiety Sanguinarine Benzodioxoles Benzophenanthridines Pharmacology Organic Chemistry DNA Isoquinolines G-Quadruplexes 030104 developmental biology Chelerythrine Complementary and alternative medicine chemistry 030220 oncology & carcinogenesis Molecular Medicine Natural alkaloids G-quadruplex Telomeric DNA Coptisine Chelerythrine Molecular modeling Crystal structure Circular dicroism |
| Zdroj: | Journal of Natural Products. 80:3128-3135 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons. In fact, the presence of a dioxolo moiety rather than the two methoxy functions improves the efficiency of coptisine and sanguinarine in comparison to berberine and chelerythrine, and the overall stability trend is sanguinarinechelerythrine ≈ coptisineberberine. Accordingly, the X-ray diffraction analysis confirmed the involvement of the benzodioxolo groups in the coptisine/DNA binding by means of π···π, O···π, and CH···O interactions. Similar information is provided by modeling studies, which, additionally, evidenced reasons for the quadruplex vs double-helix selectivity shown by these alkaloids. Thus, the analyses shed light on the key role of the benzodioxolo moieties in strengthening the interaction with the G4-folded human telomeric sequence and indicated the superior G4 stabilizing properties of the benzophenanthridine scaffold with respect to the protoberberine one and conversely the better G4 vs dsDNA selectivity profile of coptisine over the other alkaloids. |
| Databáze: | OpenAIRE |
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