In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/143306 |
Resumo: | Funding Information: Financed by Fundação para a Ciência e a Tecnologia, I.P./MCTES through national funds (PIDDAC, PT2020) under projects PTDC/MED-QUI/29036/2017, PTDC/BIA-MIC-30692/2017, EXPL/BIA-BFS/1034/2021, UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UID/Multi/04413/2020, CEECIND/03247/2018 and DL57/CEECIND/0256/2017. Publisher Copyright: Copyright © 2022 Marquês, Frazão De Faria, Reis, Machado, Santos, Santos, Viveiros, Martins and De Almeida. |
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In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosisantimycobacterial activitycytotoxicityhuman serum albumin bindingisoniazid resistancelipophilicityMycobacterium tuberculosisPharmacologyPharmacology (medical)SDG 3 - Good Health and Well-beingFunding Information: Financed by Fundação para a Ciência e a Tecnologia, I.P./MCTES through national funds (PIDDAC, PT2020) under projects PTDC/MED-QUI/29036/2017, PTDC/BIA-MIC-30692/2017, EXPL/BIA-BFS/1034/2021, UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UID/Multi/04413/2020, CEECIND/03247/2018 and DL57/CEECIND/0256/2017. Publisher Copyright: Copyright © 2022 Marquês, Frazão De Faria, Reis, Machado, Santos, Santos, Viveiros, Martins and De Almeida.The upsurge of multidrug-resistant tuberculosis has toughened the challenge to put an end to this epidemic by 2030. In 2020 the number of deaths attributed to tuberculosis increased as compared to 2019 and newly identified multidrug-resistant tuberculosis cases have been stably close to 3%. Such a context stimulated the search for new and more efficient antitubercular compounds, which culminated in the QSAR-oriented design and synthesis of a series of isoniazid derivatives active against Mycobacterium tuberculosis. From these, some prospective isonicotinoyl hydrazones and isonicotinoyl hydrazides are studied in this work. To evaluate if the chemical derivatizations are generating compounds with a good performance concerning several in vitro assays, their cytotoxicity against human liver HepG2 cells was determined and their ability to bind human serum albumin was thoroughly investigated. For the two new derivatives presented in this study, we also determined their lipophilicity and activity against both the wild type and an isoniazid-resistant strain of Mycobacterium tuberculosis carrying the most prevalent mutation on the katG gene, S315T. All compounds were less cytotoxic than many drugs in clinical use with IC50 values after a 72 h challenge always higher than 25 µM. Additionally, all isoniazid derivatives studied exhibited stronger binding to human serum albumin than isoniazid itself, with dissociation constants in the order of 10−4–10−5 M as opposed to 10−3 M, respectively. This suggests that their transport and half-life in the blood stream are likely improved when compared to the parent compound. Furthermore, our results are a strong indication that the N′ = C bond of the hydrazone derivatives of INH tested is essential for their enhanced activity against the mutant strain of M. tuberculosis in comparison to both their reduced counterparts and INH.TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)Instituto de Higiene e Medicina Tropical (IHMT)RUNMarquês, Joaquim TrigoFrazão De Faria, CatarinaReis, MarinaMachado, DianaSantos, SusanaSantos, Maria da SoledadeViveiros, MiguelMartins, FilomenaDe Almeida, Rodrigo F.M.2022-08-25T22:21:15Z2022-05-042022-05-04T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/143306eng1663-9812PURE: 45881212https://doi.org/10.3389/fphar.2022.868545info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:21:37Zoai:run.unl.pt:10362/143306Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:50:49.426379Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| title |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| spellingShingle |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis Marquês, Joaquim Trigo antimycobacterial activity cytotoxicity human serum albumin binding isoniazid resistance lipophilicity Mycobacterium tuberculosis Pharmacology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| title_short |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| title_full |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| title_fullStr |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| title_full_unstemmed |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| title_sort |
In vitro Evaluation of Isoniazid Derivatives as Potential Agents Against Drug-Resistant Tuberculosis |
| author |
Marquês, Joaquim Trigo |
| author_facet |
Marquês, Joaquim Trigo Frazão De Faria, Catarina Reis, Marina Machado, Diana Santos, Susana Santos, Maria da Soledade Viveiros, Miguel Martins, Filomena De Almeida, Rodrigo F.M. |
| author_role |
author |
| author2 |
Frazão De Faria, Catarina Reis, Marina Machado, Diana Santos, Susana Santos, Maria da Soledade Viveiros, Miguel Martins, Filomena De Almeida, Rodrigo F.M. |
| author2_role |
author author author author author author author author |
| dc.contributor.none.fl_str_mv |
TB, HIV and opportunistic diseases and pathogens (THOP) Global Health and Tropical Medicine (GHTM) Instituto de Higiene e Medicina Tropical (IHMT) RUN |
| dc.contributor.author.fl_str_mv |
Marquês, Joaquim Trigo Frazão De Faria, Catarina Reis, Marina Machado, Diana Santos, Susana Santos, Maria da Soledade Viveiros, Miguel Martins, Filomena De Almeida, Rodrigo F.M. |
| dc.subject.por.fl_str_mv |
antimycobacterial activity cytotoxicity human serum albumin binding isoniazid resistance lipophilicity Mycobacterium tuberculosis Pharmacology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| topic |
antimycobacterial activity cytotoxicity human serum albumin binding isoniazid resistance lipophilicity Mycobacterium tuberculosis Pharmacology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| description |
Funding Information: Financed by Fundação para a Ciência e a Tecnologia, I.P./MCTES through national funds (PIDDAC, PT2020) under projects PTDC/MED-QUI/29036/2017, PTDC/BIA-MIC-30692/2017, EXPL/BIA-BFS/1034/2021, UIDB/00100/2020, UIDP/00100/2020, LA/P/0056/2020, UID/Multi/04413/2020, CEECIND/03247/2018 and DL57/CEECIND/0256/2017. Publisher Copyright: Copyright © 2022 Marquês, Frazão De Faria, Reis, Machado, Santos, Santos, Viveiros, Martins and De Almeida. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-08-25T22:21:15Z 2022-05-04 2022-05-04T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/143306 |
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http://hdl.handle.net/10362/143306 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1663-9812 PURE: 45881212 https://doi.org/10.3389/fphar.2022.868545 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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