Annonalide and derivatives: Semisynthesis, cytotoxic activities and studies on interaction of annonalide with DNA
| Autor: | Edeildo Ferreira da Silva-Júnior, Isis M. Figueiredo, Fátima M. Nunes, Ricardo A. Marques, Manoel Odorico de Moraes, Ana Paula dos Santos, A. A. Leslie Gunatilaka, Ângelo de Fátima, Maria V. Brito, Josué Carinhanha Caldas Santos, Akenaton Onassis Cardoso Viana Gomes, Gladyane Santos da Silva, João Xavier de Araújo-Júnior, Maria da Conceição F. de Oliveira, Leandro Bezerra Lima, Fátima de Cássia Evangelista de Oliveira, Lucas L. Franco, Marina de Magalhães Silva, Maria Dayanne de A. Dantas, Marcos Carlos de Mattos, Thiago Mendonça de Aquino, Cláudia Pessoa |
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| Rok vydání: | 2017 |
| Předmět: |
Stereochemistry
Cell Survival Static Electricity Biophysics 010402 general chemistry 01 natural sciences chemistry.chemical_compound Cyclooctanes Cell Line Tumor Animals Humans Transition Temperature Radiology Nuclear Medicine and imaging Radiation Binding Sites Radiological and Ultrasound Technology 010405 organic chemistry DNA Ketones Semisynthesis 0104 chemical sciences Molecular Docking Simulation DNA Intercalation chemistry Docking (molecular) Spectrophotometry Nucleic Acid Conformation Thermodynamics Cattle Diterpene Drug Screening Assays Antitumor Ethidium bromide Two-dimensional nuclear magnetic resonance spectroscopy Macromolecule |
| Zdroj: | Journal of photochemistry and photobiology. B, Biology. 179 |
| ISSN: | 1873-2682 |
| Popis: | The cytotoxic activity of the pimarane diterpene annonalide (1) and nine of its semisynthetic derivatives (2–10) was investigated against the human tumor cell lines HL-60 (leukemia), PC-3 (prostate adenocarcinoma), HepG2 (hepatocellular carcinoma), SF-295 (glioblastoma) and HCT-116 (colon cancer), and normal mouse fibroblast (L929) cells. The preparation of 2–10 involved derivatization of the side chain of 1 at C-13. Except for 2, all derivatives are being reported for the first time. Most of the tested compounds presented IC50s below 4.0 μM, being considered potential antitumor agents. The structures of all new compounds were elucidated by spectroscopic analyses including 2D NMR and HRMS. Additionally, the interaction of annonalide (1) with ctDNA was evaluated using spectroscopic techniques, and the formation of a supramolecular complex with the macromolecule was confirmed. Competition assays with fluorescent probes (Hoechst and ethidium bromide) and theoretical studies confirmed that 1 interacts preferentially via DNA intercalation with stoichiometric ratio of 1:1 (1:ctDNA). The ΔG value was calculated as −28.24 kJ mol−1, and indicated that the interaction process occurs spontaneously. Docking studies revealed that van der Walls is the most important interaction in 1-DNA and EB-DNA complexes, and that both ligands (1 and EB) interact with the same DNA residues (DA6, DA17 and DT19). |
| Databáze: | OpenAIRE |
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