| Autor | Avendaño Leon, Oscar Leonardo | |
| Autor | Moncorvo, Fabiana Maia Santos Urbancg | |
| Autor | Curti, Christophe | |
| Autor | Kabri, Youssef | |
| Autor | Redon, Sébastien | |
| Autor | Vanelle, Patrice | |
| Autor | Santos, Eduardo Caio Torres dos | |
| Data de acesso | 2024-10-16T13:33:00Z | |
| Data de disponibilização | 2024-10-16T13:33:00Z | |
| Data do publicação | 2024 | |
| Citação | AVENDAÑO LEON, Oscar Leonardo et al. Hit-to-lead optimization of 4,5-dihydrofuran-3-sulfonyl scaffold against Leishmania amazonensis. Effect of an aliphatic moiety. European Journal of Medicinal Chemistry, v. 280, p. 1-12, 15 Dec. 2024. | |
| ISSN | 0223-5234 | |
| URI | https://www.arca.fiocruz.br/handle/icict/66549 | |
| Descrição | Produção científica do Laboratório de Bioquímica de Tripanossomatídeos. | pt_BR |
| Fomento | PhD Student Oscar Leonardo AVENDANO LEON was funded by COLCIENCIAS - Ministry of Science, Technology and Innovation of Colombia, Government Resolution 071 Janvier 2021 – call for PhD applications 885–2020. The antileishmanial study was supported by the FAPERJ - Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, processo E−26/201.158/2022 – BOLSA. | |
| Idioma | eng | en_US |
| Editor | Elsevier | |
| Direito Autoral | open access | |
| Título | Hit-to-lead optimization of 4,5-dihydrofuran-3-sulfonyl scaffold against Leishmania amazonensis. Effect of an aliphatic moiety | en_US |
| Tipo do documento | Article | |
| DOI | 10.1016/j.ejmech.2024.116935 | |
| Resumo em Inglês | In line with our objective of designing new antileishmanial compounds for oral use, we report the synthesis and biological evaluation in vitro of original 4,5-dihydrofuran derivatives bearing an amidoxime group. Previous optimization focused on position 3 of the dihydrofuran ring involving aromatic fragments, resulting in the identification of the compound (HIT) 4-(5-benzyl-3-((4-fluorophenyl)sulfonyl)-5-methyl-4,5-dihydrofuran-2-yl)-N′-hydroxybenzimidamide (IC₅₀ = 5.4 ± 1.0 μM, L. amazonensis promastigote, IC₅₀ = 7.9 ± 1.1 μM, L. amazonensis intracellular amastigote). In the present work, position 3 was substituted with an aliphatic moiety. This modification was guided by a ligand-based approach, given the unknown biological target or mechanism of action for this compound. The 4,5-dihydrofuran derivatives were synthesized using microwave-assisted manganese (III) acetate-based oxidative cyclization of linear β-keto-carboxylic and β-keto-sulfone substrates, overcoming synthetic challenges to obtain aliphatic derivatives of 4,5-dihydrofuran-3-carboxamides. Finally, an unexpected and interesting biological activity with the 4,5-dihydrofuran-3-carboxylate (IC₅₀ < 5 μM) against the amastigote form is discussed. | en_US |
| Afiliação | Université d'Aix-Marseille. Faculté de Pharmacie. Centre National de la Recherche Scientifique. Institut de Chimie Radicalaire. Unité Mixte de Recherche. Equipe Pharmaco-Chimie Radicalaire. Marseille, France. | |
| Afiliação | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | |
| Afiliação | Université d'Aix-Marseille. Faculté de Pharmacie. Centre National de la Recherche Scientifique. Institut de Chimie Radicalaire. Unité Mixte de Recherche. Equipe Pharmaco-Chimie Radicalaire. Marseille, France / Hôpitaux de Marseille. Assistance Publique. Hôpital de la Conception. Service Central de la Qualité et de l'Information Pharmaceutiques. Pharmacy Department. Marseille, France. | |
| Afiliação | Université d'Aix-Marseille. Faculté de Pharmacie. Centre National de la Recherche Scientifique. Institut de Chimie Radicalaire. Unité Mixte de Recherche. Equipe Pharmaco-Chimie Radicalaire. Marseille, France. | |
| Afiliação | Université d'Aix-Marseille. Faculté de Pharmacie. Centre National de la Recherche Scientifique. Institut de Chimie Radicalaire. Unité Mixte de Recherche. Equipe Pharmaco-Chimie Radicalaire. Marseille, France. | |
| Afiliação | Université d'Aix-Marseille. Faculté de Pharmacie. Centre National de la Recherche Scientifique. Institut de Chimie Radicalaire. Unité Mixte de Recherche. Equipe Pharmaco-Chimie Radicalaire. Marseille, France / Hôpitaux de Marseille. Assistance Publique. Hôpital de la Conception. Service Central de la Qualité et de l'Information Pharmaceutiques. Pharmacy Department. Marseille, France. | |
| Afiliação | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. | |
| Palavras-chave em inglês | Leishmaniasis | en_US |
| Palavras-chave em inglês | Pharmacomodulation | en_US |
| Palavras-chave em inglês | 4,5-Dihydrofuran | en_US |
| Palavras-chave em inglês | Amidoxime | en_US |
| e-ISSN | 1768-3254 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
| xmlui.metadata.dc.subject.ods | 17 Parcerias e meios de implementação | |
