| Author | Almeida-Souza, Fernando | |
| Author | Silva, Verônica Diniz da | |
| Author | Taniwaki, Noemi Nosomi | |
| Author | Hardoim, Daiana de Jesus | |
| Author | Mendonça Filho, Ailésio Rocha | |
| Author | Moreira, Wendel Fragoso de Freitas | |
| Author | Buarque, Camilla Djenne | |
| Author | Calabrese, Kátia da Silva | |
| Author | Silva, Ana Lucia Abreu | |
| Access date | 2021-11-23T12:18:01Z | |
| Available date | 2021-11-23T12:18:01Z | |
| Document date | 2021 | |
| Citation | ALMEIDA-SOUZA, Fernando Almeida et al. Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection. Journal of Medicinal Chemistry, v. 64, p. 12691-12704, Aug. 2021. | pt_BR |
| ISSN | 0022-2623 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49950 | |
| Language | eng | pt_BR |
| Publisher | American Chemical Society | pt_BR |
| Rights | restricted access | |
| Title | Nitric Oxide Induction in Peritoneal Macrophages by a 1,2,3-Triazole Derivative Improves Its Efficacy upon Leishmania amazonensis In Vitro Infection | pt_BR |
| Type | Article | |
| DOI | 10.1021/acs.jmedchem.1c00725 | |
| Abstract | 1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensis in vitro infection. After the screening of eleven compounds, compound 4 exhibited better results against L. amazonensis promastigotes (IC50 = 15.52 ± 3.782 μM) and intracellular amastigotes (IC50 = 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4 induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensis promastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p = 0.0095) and inducible nitric oxide synthase expression (p = 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silico prediction in association with antileishmanial activity results showed compound 4 as a hit compound with promising potential for further studies of new leishmaniasis treatment options. | pt_BR |
| Affilliation | Universidade Estadual do Maranhão. Departamento de Patologia. Laboratório de Anatomopatologia. São Luís, MA, Brasil. | pt_BR |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Laboratório de Sintese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Adolfo Lutz. Núcleo de Microscopia Eletrônica. São Paulo, SP, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Estadual do Maranhão. Departamento de Patologia. Laboratório de Anatomopatologia. São Luís, MA, Brasil. | pt_BR |
| Affilliation | Universidade Estadual do Maranhão. Departamento de Patologia. Laboratório de Anatomopatologia. São Luís, MA, Brasil. | pt_BR |
| Affilliation | Pontifícia Universidade Católica do Rio de Janeiro. Laboratório de Sintese Orgânica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Estadual do Maranhão. Departamento de Patologia. Laboratório de Anatomopatologia. São Luís, MA, Brasil. | pt_BR |
| Subject | Nitric Oxide Induction | pt_BR |
| Subject | Peritoneal Macrophages | pt_BR |
| Subject | Triazoles | pt_BR |
| Subject | Efficacy | pt_BR |
| Subject | Leishmania amazonensis | pt_BR |
| Subject | In Vitro Infection | pt_BR |
| e-ISSN | 1520-4804 | |
| Embargo date | 2030-12-31 | |
