Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria

Detalhes bibliográficos
Autor(a) principal: Touitou, Meir
Data de Publicação: 2020
Outros Autores: Manetti, Fabrizio, Ribeiro, Camila Maringolo [UNESP], Pavan, Fernando Rogerio [UNESP], Scalacci, Nicolò, Zrebna, Katarina, Begum, Neelu, Semenya, Dorothy, Gupta, Antima, Bhakta, Sanjib, Mchugh, Timothy D., Senderowitz, Hanoch, Kyriazi, Melina, Castagnolo, Daniele
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1021/acsmedchemlett.9b00515
http://hdl.handle.net/11449/201456
Resumo: A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.
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spelling Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteriaantimycobacterial drugdrug resistanceintracellular tuberculosispyrrolesTuberculosisA series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.School of Cancer and Pharmaceutical Sciences King's College London, 150 Stamford StreetDipartimento di Biotecnologie Chimica e Farmacia, via A. Moro 2Tuberculosis Research Laboratory School of Pharmaceutical Sciences Sao Paulo State University (UNESP), Rod. Araraquara-Jau, km1Centre for Clinical Microbiology University College LondonMycobacteria Research Laboratory Department of Biological Sciences Institute of Structural and Molecular Biology Birkbeck University of London, Malet StreetDepartment of Chemistry Faculty of Exact Sciences Bar-Ilan UniversityTuberculosis Research Laboratory School of Pharmaceutical Sciences Sao Paulo State University (UNESP), Rod. Araraquara-Jau, km1King's College LondonChimica e FarmaciaUniversidade Estadual Paulista (Unesp)University College LondonUniversity of LondonBar-Ilan UniversityTouitou, MeirManetti, FabrizioRibeiro, Camila Maringolo [UNESP]Pavan, Fernando Rogerio [UNESP]Scalacci, NicolòZrebna, KatarinaBegum, NeeluSemenya, DorothyGupta, AntimaBhakta, SanjibMchugh, Timothy D.Senderowitz, HanochKyriazi, MelinaCastagnolo, Daniele2020-12-12T02:32:59Z2020-12-12T02:32:59Z2020-05-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article638-644http://dx.doi.org/10.1021/acsmedchemlett.9b00515ACS Medicinal Chemistry Letters, v. 11, n. 5, p. 638-644, 2020.1948-5875http://hdl.handle.net/11449/20145610.1021/acsmedchemlett.9b005152-s2.0-85077653042Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengACS Medicinal Chemistry Lettersinfo:eu-repo/semantics/openAccess2024-06-24T13:06:59Zoai:repositorio.unesp.br:11449/201456Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:42:44.445560Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
title Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
spellingShingle Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
Touitou, Meir
antimycobacterial drug
drug resistance
intracellular tuberculosis
pyrroles
Tuberculosis
title_short Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
title_full Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
title_fullStr Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
title_full_unstemmed Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
title_sort Improving the Potency of N-Aryl-2,5-dimethylpyrroles against Multidrug-Resistant and Intracellular Mycobacteria
author Touitou, Meir
author_facet Touitou, Meir
Manetti, Fabrizio
Ribeiro, Camila Maringolo [UNESP]
Pavan, Fernando Rogerio [UNESP]
Scalacci, Nicolò
Zrebna, Katarina
Begum, Neelu
Semenya, Dorothy
Gupta, Antima
Bhakta, Sanjib
Mchugh, Timothy D.
Senderowitz, Hanoch
Kyriazi, Melina
Castagnolo, Daniele
author_role author
author2 Manetti, Fabrizio
Ribeiro, Camila Maringolo [UNESP]
Pavan, Fernando Rogerio [UNESP]
Scalacci, Nicolò
Zrebna, Katarina
Begum, Neelu
Semenya, Dorothy
Gupta, Antima
Bhakta, Sanjib
Mchugh, Timothy D.
Senderowitz, Hanoch
Kyriazi, Melina
Castagnolo, Daniele
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv King's College London
Chimica e Farmacia
Universidade Estadual Paulista (Unesp)
University College London
University of London
Bar-Ilan University
dc.contributor.author.fl_str_mv Touitou, Meir
Manetti, Fabrizio
Ribeiro, Camila Maringolo [UNESP]
Pavan, Fernando Rogerio [UNESP]
Scalacci, Nicolò
Zrebna, Katarina
Begum, Neelu
Semenya, Dorothy
Gupta, Antima
Bhakta, Sanjib
Mchugh, Timothy D.
Senderowitz, Hanoch
Kyriazi, Melina
Castagnolo, Daniele
dc.subject.por.fl_str_mv antimycobacterial drug
drug resistance
intracellular tuberculosis
pyrroles
Tuberculosis
topic antimycobacterial drug
drug resistance
intracellular tuberculosis
pyrroles
Tuberculosis
description A series of N-phenyl-2,5-dimethylpyrrole derivatives, designed as hybrids of the antitubercular agents BM212 and SQ109, have been synthesized and evaluated against susceptible and drug-resistant mycobacteria strains. Compound 5d, bearing a cyclohexylmethylene side chain, showed high potency against M. tuberculosis including MDR-TB strains at submicromolar concentrations. The new compound shows bacteriostatic activity and low toxicity and proved to be effective against intracellular mycobacteria too, showing an activity profile similar to isoniazid.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-12T02:32:59Z
2020-12-12T02:32:59Z
2020-05-14
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1021/acsmedchemlett.9b00515
ACS Medicinal Chemistry Letters, v. 11, n. 5, p. 638-644, 2020.
1948-5875
http://hdl.handle.net/11449/201456
10.1021/acsmedchemlett.9b00515
2-s2.0-85077653042
url http://dx.doi.org/10.1021/acsmedchemlett.9b00515
http://hdl.handle.net/11449/201456
identifier_str_mv ACS Medicinal Chemistry Letters, v. 11, n. 5, p. 638-644, 2020.
1948-5875
10.1021/acsmedchemlett.9b00515
2-s2.0-85077653042
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ACS Medicinal Chemistry Letters
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 638-644
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
_version_ 1808128407992532992

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