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| Autor | Sousa, Caroline C | |
| Autor | Dziwornu, Godwin Akpeko | |
| Autor | Quadros, Helenita C | |
| Autor | Araújo Neto, João Honorato | |
| Autor | Chibale, Kelly | |
| Autor | Moreira, Diogo R. M | |
| Fecha de acceso | 2022-09-28T17:54:26Z | |
| Fecha de disponibilización | 2022-09-28T17:54:26Z | |
| Fecha de publicación | 2022 | |
| Referencia | SOUSA, Caroline C. et al. Antimalarial pyrido [1,2‑a] benzimidazoles exert strong parasiticidal effects by achieving high cellular uptake and suppressing heme detoxification. ACS Infectious Diseases, v. 8, p. 1-11, 2022. | en_US |
| ISSN | 2373-8227 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/54917 | |
| Promoción | Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). Fundação Oswaldo Cruz (Fiocruz) / Programa de Excelência em Pesquisa (PROEP). University of Cape Town. South African Medical Research Council. South African Research Chairs Initiative of the Department of Science and Innovation. South African National Research Foundation. | en_US |
| Idioma | eng | en_US |
| Editor | American Chemical Society | en_US |
| Derechos de autor | open access | en_US |
| MeSH | Malaria | en_US |
| MeSH | Plasmodium | en_US |
| Palabras clave en Portugués | Malária | en_US |
| Palabras clave en Portugués | Plasmodium | en_US |
| Palabras clave en Portugués | Benzimidazol | en_US |
| Palabras clave en Portugués | Parasiticida | en_US |
| Palabras clave en Portugués | Heme pool | en_US |
| Palabras clave en Portugués | Desintoxicação do heme | en_US |
| Título | Antimalarial pyrido [1,2‑a] benzimidazoles exert strong parasiticidal effects by achieving high cellular uptake and suppressing heme detoxification | en_US |
| Tipo del documento | Article | en_US |
| DOI | 10.1021/acsinfecdis.2c00326 | |
| Resumen en Inglés | Pyrido[1,2-a]benzimidazoles (PBIs) are synthetic antiplasmodium agents with potent activity and are structurally differentiated from benchmark antimalarials. To study the cellular uptake of PBIs and understand the underlying phenotype of their antiplasmodium activity, their antiparasitic activities were examined in chloroquine (CQ)-susceptible and CQ-resistant Plasmodium falciparumin vitro. Moreover, drug uptake and heme detoxification suppression were examined in Plasmodium berghei-infected mice. The in vitro potency of PBIs is comparable to most 4-aminoquinolines. They have a speed of action in vitro that is superior to that of atovaquone and an ability to kill rings and trophozoites. The antiparasitic effects observed for the PBIs in cell culture and in infected mice are similar in terms of potency and efficacy and are comparable to CQ but with the added advantage of demonstrating equipotency against both CQ susceptible and resistant parasite strains. PBIs have a high rate of uptake by parasite cells and, conversely, a limited rate of uptake by host cells. The mechanism of cellular uptake of the PBIs differs from the ion-trap mechanism typically observed for 4-aminoquinolines, although they share key structural features. The high cellular uptake, attractive parasiticidal profile, and susceptibility of resistant strains to PBIs are desirable characteristics for new antimalarial agents. | en_US |
| Afiliación | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz, Salvador, BA, Brasil. | en_US |
| Afiliación | South African Medical Research Council Drug Discovery and Development Research Unit, Department of Chemistry and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town. Rondebosch, South Africa | en_US |
| Afiliación | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz, Salvador, BA, Brasil. | en_US |
| Afiliación | Universidade de São Paulo. São Paulo, SP, Brasil. | en_US |
| Afiliación | South African Medical Research Council Drug Discovery and Development Research Uni., Department of Chemistry and Institute of Infectious Diseases and Molecular Medicine. University of Cape Town. Rondebosch, South Africa | en_US |
| Afiliación | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz, Salvador, BA, Brasil. | en_US |
| Palavras clave en Inglês | Malaria | en_US |
| Palavras clave en Inglês | Plasmodium | en_US |
| Palavras clave en Inglês | Benzimidazole | en_US |
| Palavras clave en Inglês | Parasiticidal | en_US |
| Palavras clave en Inglês | Heme pool | en_US |
| Palavras clave en Inglês | Heme detoxification | en_US |
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