| Author | Carneiro, Leonardo S. A. | |
| Author | Souza, Fernando Almeida | |
| Author | Lopes, Yanne S. C. | |
| Author | Novas, Rachel C.V. | |
| Author | Santos, Kaique Bertrand Almeida | |
| Author | Ligiero, Carolina B. P. | |
| Author | Calabrese, Kátia da Silva | |
| Author | Buarque, Camilla D. | |
| Access date | 2021-07-19T17:06:09Z | |
| Available date | 2021-07-19T17:06:09Z | |
| Document date | 2021 | |
| Citation | CARNEIRO, Leonardo S. A. et al. Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity. Journal Pre-proofs, p. 1-45, 2021. | |
| URI | https://www.arca.fiocruz.br/handle/icict/48281 | |
| Language | eng | en_US |
| Publisher | Elsevier | |
| Rights | restricted access | |
| Subject in Portuguese | Difração de Raios X | pt_BR |
| Subject in Portuguese | Leishmaniose | pt_BR |
| Subject in Portuguese | Citotoxidade | pt_BR |
| Subject in Portuguese | Farmacocinética | pt_BR |
| Title | Synthesis of 3-aryl-4-(N-aryl)aminocoumarins via photoredox arylation and the evaluation of their biological activity | en_US |
| Type | Preprint | |
| DOI | 10.1016/j.bioorg.2021.105141 | |
| Abstract | A new series of 3-aryl-4-(N-aryl)aminocoumarins was synthesized in two steps starting from the natural product 4-hydroxycoumarin using the photoredox catalysis for the key step. These conditions reactions allowed to make C-C bonds is up to 95% yields in mild conditions, easy operation, in an environmentally benign way, and are compatible with several patterns of substitution. The biological activity of the new compounds was tested in vitro against MCF-7, MDA-MB-231, and CCD-1072Sk cancer cell lines, as soon as to promastigotes and intracellular amastigotes of Leishmania amazonensis. Compounds 17d, 17s and 17x showed activity against promastigote forms (IC50 = 5.96 ± 3.210, 9.05 ± 2.855 and 5.65 ± 2.078 μM respectively), and compound 17x presented the best activity against L. amazonensis amastigote intracellular form (IC50 = 9.6 ± 1.148 μM), no BALB/c peritoneal macrophage cytotoxicity at assayed concentrations (CC50 > 600 μM), and high selectivity to parasites over the mammalian cells (Selectivity Index > 62.2). There was no expressive activity for the cancer cell lines. Single crystal X-ray diffraction analysis was employed for structural elucidation of compounds 17a and 17s. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compound 17x is a potential candidate for anti-leishmaniasis drugs. | en_US |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Departamento de Química. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luis, MA, Brasil / Fundação Oswaldo Cruz, Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Departamento de Química. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Departamento de Química. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Departamento de Química. Rio de Janeiro, RJ, Brasil. | |
| Subject | Aminocoumarin | en_US |
| Subject | Arylation | en_US |
| Subject | Arylcoumarin | en_US |
| Subject | Photoredox catalysis | en_US |
| Subject | X-ray diffraction | en_US |
| Subject | Leishmaniasis | en_US |
| Subject | Cytotoxicity | en_US |
| Subject | in silico | en_US |
| Subject | ADMET | en_US |
| DeCS | Difração de Raios X | pt_BR |
| DeCS | Citotoxicidade Celular Dependente de Anticorpos | pt_BR |
| DeCS | Modelos Computacionais | pt_BR |
| DeCS | Farmacocinética | pt_BR |
| Embargo date | 2023 | |
