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http://hdl.handle.net/1843/76543| Type: | Artigo de Periódico |
| Title: | Annonalide and derivatives: semisynthesis, cytotoxic activities and studies on interaction of annonalide with DNA |
| Authors: | Ricardo de Araujo Marques Cláudia Do Ó Pessoa Manoel Odorico de Moraes Filho Ângelo de Fátima Lucas Lopardi Franco Marina de Magalhães Silva Maria Dayanne de Araújo Dantas Josué Carinhanha Caldas Santos Isis Martins Figueiredo Edeildo Ferreira da Silva-Júnior Thiago Mendonça de Aquino Akenaton Onassis Cardoso Viana Gomes João Xavier de Araújo-Júnior Maria da Conceição Ferreira de Oliveira Abeysinghe Aleslie Gunatilaka Maria Vieira de Brito Ana L. P. dos Santos Gladyane Santos da Silva Leandro Bezerra de Lima Fátima Miranda Nunes Marcos Carlos de Mattos Fátima de Cássia Evangelista de Oliveira |
| Abstract: | 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). |
| Subject: | DNA Diterpenos Agentes antineoplásicos Citotoxidade de mediação celular Funcionais de densidade |
| language: | eng |
| metadata.dc.publisher.country: | Brasil |
| Publisher: | Universidade Federal de Minas Gerais |
| Publisher Initials: | UFMG |
| metadata.dc.publisher.department: | ICX - DEPARTAMENTO DE QUÍMICA |
| Rights: | Acesso Restrito |
| metadata.dc.identifier.doi: | https://doi.org/10.1016/j.jphotobiol.2018.01.016 |
| URI: | http://hdl.handle.net/1843/76543 |
| Issue Date: | 2018 |
| metadata.dc.url.externa: | https://www.sciencedirect.com/science/article/pii/S1011134417313441 |
| metadata.dc.relation.ispartof: | Journal of Photochemistry and Photobiology B: Biology |
| Appears in Collections: | Artigo de Periódico |
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