| Author | Santos Filho, José Maurício dos | |
| Author | Silva, Diogo Manoel Alves de Queiroz e | |
| Author | Macedo, Taís Soares | |
| Author | Teixeira, Helena Mariana Pitangueira | |
| Author | Moreira, Diogo Rodrigo Magalhães | |
| Author | Challal, Soura | |
| Author | Wolfender, Jean-Luc | |
| Author | Queiroz, Emerson Ferreira | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2016-12-26T19:00:41Z | |
| Available date | 2016-12-26T19:00:41Z | |
| Document date | 2016 | |
| Citation | SANTOS FILHO, José Maurício dos et al. Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents. Bioorganic & Medicinal Chemistry, p. 1-9, Nov. 2016. | pt_BR |
| ISSN | 0968-0896 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/16563 | |
| Sponsorship | FAPESB | pt_BR |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | Malária | pt_BR |
| Subject in Portuguese | Plasmodium falciparum | pt_BR |
| Subject in Portuguese | Drogas | pt_BR |
| Subject in Portuguese | Oxidiazóis | pt_BR |
| Title | Conjugation of N-acylhydrazone and 1,2,4-oxadiazole leads to the identification of active antimalarial agents | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.bmc.2016.09.013 | |
| Abstract | Malaria, caused by several Plasmodium species, is the major life-threatening parasitic infection worldwide. Due to the parasite resistance to quinoline based drugs, the search for antimalarial agents is necessary. Here, we report the structural design, synthesis and antiparasitic evaluation of two novel series of 1,2,4-oxadiazoles in conjugation to N-acylhydrazones, both groups recognized as privileged structures, as well as the studies on the antimalarial activity of 16 previous described analogues. By varying substituents attached to the phenyl ring, it was possible to retain, enhance or increase the antiparasitic activity in comparison to the nonsubstituted derivatives. Replacement of substituted aryl rings by ferrocenyl and cinnamyl moieties attached in the N-acylhydrazone ablated the antiparasitic response, evidencing the structural features associated with the activity. Active compounds exhibited in vitro potency similar to mefloquine, but not all inhibited β-hematin formation. Additionally, the active compounds displayed low cytotoxicity in HepG2 cells and did not cause hemolysis in uninfected erythrocytes. In Plasmodium berghei-infected mice, the compounds reduced parasitemia but exhibited limited efficacy in increasing mice survival when compared to chloroquine, suggesting that pharmacological improvement is still necessary. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Centro de Tecnologia e Geociências. Laboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed . Recife, PE, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pernambuco. Centro de Tecnologia e Geociências. Laboratory of Design and Synthesis Applied to Medicinal Chemistry-SintMed . Recife, PE, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. EPGL. Geneva, Switzerland. | pt_BR |
| Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. EPGL. Geneva, Switzerland. | pt_BR |
| Affilliation | University of Geneva. University of Lausanne. School of Pharmaceutical Sciences. EPGL. Geneva, Switzerland. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil. | pt_BR |
| Subject | Malaria | pt_BR |
| Subject | Plasmodium falciparum | pt_BR |
| Subject | Drug design | pt_BR |
| Subject | Oxadiazoles | pt_BR |
| Embargo date | 2030-12-31 | |
