| Author | Sousa, Gleyton | |
| Author | Almeida, Maria C. F. de | |
| Author | Lócio, Lucas L. | |
| Author | Santos, Vanda L. dos | |
| Author | Bezerra, Daniel P. | |
| Author | Silva, Valdenizia R. | |
| Author | Almeida, Sinara M. V. de | |
| Author | Simon, Alice | |
| Author | Honório, Thiago da S. | |
| Author | Cabral, Lucio M. | |
| Author | Castro, Rosane N. | |
| Author | Moura, Ricardo O. de | |
| Author | Kümmerle, Arthur E. | |
| Access date | 2023-01-10T12:16:29Z | |
| Available date | 2023-01-10T12:16:29Z | |
| Document date | 2022 | |
| Citation | SOUSA, Gleyton et al. Synthesis and evaluation of antiproliferative activity, topoisomerase II inhibition, DNA binding and non-clinical toxicity of new acridine–thiosemicarbazone derivatives. Pharmaceuticals, v. 15, p. 1-26, 2022. | en_US |
| ISSN | 1424-8247 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/56417 | |
| Sponsorship | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).
Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). | en_US |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Acridina-tiosemicarbazona | en_US |
| Subject in Portuguese | Antiproliferativo | en_US |
| Subject in Portuguese | Topoisomerase II | en_US |
| Title | Synthesis and evaluation of antiproliferative activity, topoisomerase II inhibition, DNA binding and non-clinical toxicity of new acridine–thiosemicarbazone derivatives | en_US |
| Type | Article | en_US |
| DOI | 10.3390/ ph15091098 | |
| Abstract | In this study, we report the synthesis of twenty new acridine–thiosemicarbazone derivatives and their antiproliferative activities. Mechanisms of action such as the inhibition of topoisomerase II and the interaction with DNA have been studied for some of the most active derivatives by means of both in silico and in vitro methods, and evaluations of the non-clinical toxicities (in vivo) in mice. In general, the compounds showed greater cytotoxicity against B16-F10 cells, with the highest potency for DL-08 (IC50 = 14.79 M). Derivatives DL-01 (77%), DL-07 (74%) and DL-08 (79%) showed interesting inhibition of topoisomerase II when compared to amsacrine, at 100 M. In silico studies proposed the way of bonding of these compounds and a possible stereoelectronic reason for the absence of enzymatic activity for CL-07 and DL-06. Interactions with DNA presented different spectroscopic effects and indicate that the compound CL-07 has higher affinity for DNA (Kb = 4.75 104 M1; Ksv = 2.6 103 M1). In addition, compounds selected for non-clinical toxicity testing did not show serious signs of toxicity at the dose of 2000 mg/kg in mice; cytotoxic tests performed on leukemic cells (K-562) and its resistant form (K-562 Lucena 1) identified moderate potency for DL-01 and DL-08, with IC50 between 11.45 and 17.32 M. | en_US |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Química. Seropédica, RJ, Brasil / Universidade Estadual da Paraíba. Departamento de Química. Campina Grande, PB, Brasil. | en_US |
| Affilliation | Universidade Estadual da Paraíba. Departamento de Ciências Biológicas. Campina Grande, PB, Brasil. | en_US |
| Affilliation | Universidade Estadual da Paraíba. Departamento de Ciências Biológicas. Campina Grande, PB, Brasil. | en_US |
| Affilliation | Universidade Estadual da Paraíba. Departamento de Ciências Biológicas. Campina Grande, PB, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia de Tecidos e Imunofarmacologia. Salvador, BA, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório de Engenharia de Tecidos e Imunofarmacologia. Salvador, BA, Brasil. | en_US |
| Affilliation | Universidade de Pernambuco. Laboratório de Biologia Molecular. Garanhuns, PE, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Medicamentos e Farmacêutica. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Medicamentos e Farmacêutica. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Medicamentos e Farmacêutica. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Química. Seropédica, RJ, Brasil. | en_US |
| Affilliation | Universidade Estadual da Paraíba. Departamento de Ciências Biológicas. Campina Grande, PB, Brasil. | en_US |
| Affilliation | Universidade Federal Rural do Rio de Janeiro. Instituto de Química. Seropédica, RJ, Brasil. | en_US |
| Subject | Acridine–thiosemicarbazone | en_US |
| Subject | Antiproliferative | en_US |
| Subject | Topoisomerase II | en_US |
| DeCS | Acridina | en_US |
| DeCS | Tiosemicarbazona | en_US |
| DeCS | DNA Topoisomerases Tipo II | en_US |
