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Synthesis and biological activity against Mycobacterium tuberculosis of 2,3-dihydroadenine derivatives

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Detalhes bibliográficos
Resumo:Purines have attracted attention of the scientific community mainly due to their biological activity [1]. During the last decade, purine derivatives were identified as a promising new class of antitubercular agents. The research was focused on the synthesis of nucleoside analogues as siderophore biosynthesis inhibitors [2], and on non-nucleosides [3]. In the non-nucleoside series, purines having an aryl, a small alkyl or a proton as the 9-N substituent were essentially inactive, whereas 9-benzyl-6-(2-furyl)purines [3a,c,d], 9-sulfonyl-6-mercaptopurines or 6-alkylthiopurines [3b,e] were highly potent. In addition, we recently described the first example of 2,9-diarylpurines active against Mycobacterium tuberculosis (Mtb) [4]. In order to perform SAR studies in the new scaffold, we synthesized novel 2,3-dihydroadenine derivatives. These new molecules represent valuable targets as they possess all the sub units present in the 2-phenolic adenine derivatives that showed activity against Mtb however they allow new conformations. The synthesis of the new derivatives and the biological results obtained against Mtb will be presented.
Autores principais:Correia, Carla
Outros Autores:Proença, M. Fernanda R. P.; Carvalho, M. Alice
Assunto:Ciências Naturais::Ciências Químicas
Ano:2017
País:Portugal
Tipo de documento:póster em conferência
Tipo de acesso:acesso restrito
Instituição associada:Universidade do Minho
Idioma:inglês
Origem:RepositóriUM - Universidade do Minho
Descrição
Resumo:Purines have attracted attention of the scientific community mainly due to their biological activity [1]. During the last decade, purine derivatives were identified as a promising new class of antitubercular agents. The research was focused on the synthesis of nucleoside analogues as siderophore biosynthesis inhibitors [2], and on non-nucleosides [3]. In the non-nucleoside series, purines having an aryl, a small alkyl or a proton as the 9-N substituent were essentially inactive, whereas 9-benzyl-6-(2-furyl)purines [3a,c,d], 9-sulfonyl-6-mercaptopurines or 6-alkylthiopurines [3b,e] were highly potent. In addition, we recently described the first example of 2,9-diarylpurines active against Mycobacterium tuberculosis (Mtb) [4]. In order to perform SAR studies in the new scaffold, we synthesized novel 2,3-dihydroadenine derivatives. These new molecules represent valuable targets as they possess all the sub units present in the 2-phenolic adenine derivatives that showed activity against Mtb however they allow new conformations. The synthesis of the new derivatives and the biological results obtained against Mtb will be presented.