Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines
Tuberculosis remains a global health problem that affects millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 <i>N</i>-(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their abili...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/8/2556 |
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| author | Estevão Silveira Grams Alessandro Silva Ramos Mauro Neves Muniz Raoní S. Rambo Marcia Alberton Perelló Nathalia Sperotto Laura Calle González Lovaine Silva Duarte Luiza Galina Adilio Silva Dadda Guilherme Arraché Gonçalves Cristiano Valim Bizarro Luiz Augusto Basso Pablo Machado |
| author_facet | Estevão Silveira Grams Alessandro Silva Ramos Mauro Neves Muniz Raoní S. Rambo Marcia Alberton Perelló Nathalia Sperotto Laura Calle González Lovaine Silva Duarte Luiza Galina Adilio Silva Dadda Guilherme Arraché Gonçalves Cristiano Valim Bizarro Luiz Augusto Basso Pablo Machado |
| author_sort | Estevão Silveira Grams |
| collection | DOAJ |
| description | Tuberculosis remains a global health problem that affects millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 <i>N</i>-(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their ability to inhibit the <i>M. tuberculosis</i> H37Rv strain. Two of these compounds exhibited minimal inhibitory concentrations (MICs) similar to the first-line drug isoniazid. In addition, these hit compounds were selective for the bacillus with no significant change in viability of Vero and HepG2 cells. Finally, chemical stability, permeability and metabolic stability were also evaluated. The obtained data show that the molecular hits can be optimized aiming at the development of drug candidates for tuberculosis treatment. |
| first_indexed | 2024-03-09T04:21:11Z |
| format | Article |
| id | doaj.art-aef2189898f3466dbf2421b59ab0d6b7 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:21:11Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aef2189898f3466dbf2421b59ab0d6b72023-12-03T13:46:54ZengMDPI AGMolecules1420-30492022-04-01278255610.3390/molecules27082556Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolinesEstevão Silveira Grams0Alessandro Silva Ramos1Mauro Neves Muniz2Raoní S. Rambo3Marcia Alberton Perelló4Nathalia Sperotto5Laura Calle González6Lovaine Silva Duarte7Luiza Galina8Adilio Silva Dadda9Guilherme Arraché Gonçalves10Cristiano Valim Bizarro11Luiz Augusto Basso12Pablo Machado13Instituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilInstituto Nacional de Ciência e Tecnologia em Tuberculose, Centro de Pesquisas em Biologia Molecular e Funcional, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre 90619-900, RS, BrazilTuberculosis remains a global health problem that affects millions of people around the world. Despite recent efforts in drug development, new alternatives are required. Herein, a series of 27 <i>N</i>-(4-(benzyloxy)benzyl)-4-aminoquinolines were synthesized and evaluated for their ability to inhibit the <i>M. tuberculosis</i> H37Rv strain. Two of these compounds exhibited minimal inhibitory concentrations (MICs) similar to the first-line drug isoniazid. In addition, these hit compounds were selective for the bacillus with no significant change in viability of Vero and HepG2 cells. Finally, chemical stability, permeability and metabolic stability were also evaluated. The obtained data show that the molecular hits can be optimized aiming at the development of drug candidates for tuberculosis treatment.https://www.mdpi.com/1420-3049/27/8/2556<i>Mycobacterium tuberculosis</i>drug discoverysynthesisquinolinestuberculosis |
| spellingShingle | Estevão Silveira Grams Alessandro Silva Ramos Mauro Neves Muniz Raoní S. Rambo Marcia Alberton Perelló Nathalia Sperotto Laura Calle González Lovaine Silva Duarte Luiza Galina Adilio Silva Dadda Guilherme Arraché Gonçalves Cristiano Valim Bizarro Luiz Augusto Basso Pablo Machado Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines Molecules <i>Mycobacterium tuberculosis</i> drug discovery synthesis quinolines tuberculosis |
| title | Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines |
| title_full | Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines |
| title_fullStr | Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines |
| title_full_unstemmed | Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines |
| title_short | Synthesis and Antimycobacterial Evaluation of <i>N</i>-(4-(Benzyloxy)benzyl)-4-aminoquinolines |
| title_sort | synthesis and antimycobacterial evaluation of i n i 4 benzyloxy benzyl 4 aminoquinolines |
| topic | <i>Mycobacterium tuberculosis</i> drug discovery synthesis quinolines tuberculosis |
| url | https://www.mdpi.com/1420-3049/27/8/2556 |
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