Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii

Detalhes bibliográficos
Autor(a) principal: Gionbelli, Mariana Pies
Data de Publicação: 2019
Tipo de documento: Trabalho de conclusão de curso
Idioma: eng
Título da fonte: Repositório Institucional da UFRGS
Texto Completo: http://hdl.handle.net/10183/238133
Resumo: Cryptococcosis is an important infectious disease, mainly because the increasing prevalence in recent decades and resistance treatment. Development of new drugs for the treatment of this disease is imperative. Recent studies from our research group revealed significant antimicrobial activity of 5-substituted 8-hydroxyquinoline derivatives as 8-hydroxy-5-quinolinesulfonic acid and 8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide. Therefore, in order to study the structure activity relationships (SAR) of these compounds, sulfonamide derivatives of 8-hydroxyquinoline were synthesized varying the substitution on the 5-sulfonamide and also inverting the sulfonamide group. Derivatives of 8-hydroxyquinoline-5-sulfonyl chloride and 5-aminoquinolin-8-ol were obtained for in vitro screening against Cryptococcus neoformans and C. gattii using broth microdilution method. Compound 3a was the most active derivative of this series, demonstrating activity over 2-fold better than fluconazole against C. neoformans. Derivatives 3b and 3c were equally actives, but not as potent as 3a. The position inversion of the sulfonamide resulted in reduced activity of derivatives 6a and 6b, emphasizing the importance of the sulfonyl group position in the molecule. Finally, the 3-series derivatives can be promising antifungal candidates to treat cryptococcosis.
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spelling Gionbelli, Mariana PiesAndrade, Saulo Fernandes de2022-05-03T04:49:54Z2019http://hdl.handle.net/10183/238133001114769Cryptococcosis is an important infectious disease, mainly because the increasing prevalence in recent decades and resistance treatment. Development of new drugs for the treatment of this disease is imperative. Recent studies from our research group revealed significant antimicrobial activity of 5-substituted 8-hydroxyquinoline derivatives as 8-hydroxy-5-quinolinesulfonic acid and 8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide. Therefore, in order to study the structure activity relationships (SAR) of these compounds, sulfonamide derivatives of 8-hydroxyquinoline were synthesized varying the substitution on the 5-sulfonamide and also inverting the sulfonamide group. Derivatives of 8-hydroxyquinoline-5-sulfonyl chloride and 5-aminoquinolin-8-ol were obtained for in vitro screening against Cryptococcus neoformans and C. gattii using broth microdilution method. Compound 3a was the most active derivative of this series, demonstrating activity over 2-fold better than fluconazole against C. neoformans. Derivatives 3b and 3c were equally actives, but not as potent as 3a. The position inversion of the sulfonamide resulted in reduced activity of derivatives 6a and 6b, emphasizing the importance of the sulfonyl group position in the molecule. Finally, the 3-series derivatives can be promising antifungal candidates to treat cryptococcosis.application/pdfengOxiquinolinaAntifúngicosCriptococoseSulfonamidasFarmácia8-hydroxyquinoline derivativesCryptococcosisAntifungal activitySynthesisSulfonamidesEffects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattiiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/bachelorThesisUniversidade Federal do Rio Grande do SulFaculdade de FarmáciaPorto Alegre, BR-RS2019Farmáciagraduaçãoinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001114769.pdf.txt001114769.pdf.txtExtracted Texttext/plain30735http://www.lume.ufrgs.br/bitstream/10183/238133/2/001114769.pdf.txta380bb0149515095574dc94efdcee7d9MD52ORIGINAL001114769.pdfTexto completoapplication/pdf1529825http://www.lume.ufrgs.br/bitstream/10183/238133/1/001114769.pdf8cd4c254bbf6f80373a4b161be899812MD5110183/2381332022-05-04 04:45:26.976916oai:www.lume.ufrgs.br:10183/238133Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-05-04T07:45:26Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false
dc.title.pt_BR.fl_str_mv Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
title Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
spellingShingle Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
Gionbelli, Mariana Pies
Oxiquinolina
Antifúngicos
Criptococose
Sulfonamidas
Farmácia
8-hydroxyquinoline derivatives
Cryptococcosis
Antifungal activity
Synthesis
Sulfonamides
title_short Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
title_full Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
title_fullStr Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
title_full_unstemmed Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
title_sort Effects of inversion or substitution of the sulfonamide group at 5-position of 8-hydroxyquinoline derivatives against Cryptococcus neoformans and C. gattii
author Gionbelli, Mariana Pies
author_facet Gionbelli, Mariana Pies
author_role author
dc.contributor.author.fl_str_mv Gionbelli, Mariana Pies
dc.contributor.advisor1.fl_str_mv Andrade, Saulo Fernandes de
contributor_str_mv Andrade, Saulo Fernandes de
dc.subject.por.fl_str_mv Oxiquinolina
Antifúngicos
Criptococose
Sulfonamidas
Farmácia
topic Oxiquinolina
Antifúngicos
Criptococose
Sulfonamidas
Farmácia
8-hydroxyquinoline derivatives
Cryptococcosis
Antifungal activity
Synthesis
Sulfonamides
dc.subject.eng.fl_str_mv 8-hydroxyquinoline derivatives
Cryptococcosis
Antifungal activity
Synthesis
Sulfonamides
description Cryptococcosis is an important infectious disease, mainly because the increasing prevalence in recent decades and resistance treatment. Development of new drugs for the treatment of this disease is imperative. Recent studies from our research group revealed significant antimicrobial activity of 5-substituted 8-hydroxyquinoline derivatives as 8-hydroxy-5-quinolinesulfonic acid and 8-hydroxyquinoline-5-(N-4-chlorophenyl) sulfonamide. Therefore, in order to study the structure activity relationships (SAR) of these compounds, sulfonamide derivatives of 8-hydroxyquinoline were synthesized varying the substitution on the 5-sulfonamide and also inverting the sulfonamide group. Derivatives of 8-hydroxyquinoline-5-sulfonyl chloride and 5-aminoquinolin-8-ol were obtained for in vitro screening against Cryptococcus neoformans and C. gattii using broth microdilution method. Compound 3a was the most active derivative of this series, demonstrating activity over 2-fold better than fluconazole against C. neoformans. Derivatives 3b and 3c were equally actives, but not as potent as 3a. The position inversion of the sulfonamide resulted in reduced activity of derivatives 6a and 6b, emphasizing the importance of the sulfonyl group position in the molecule. Finally, the 3-series derivatives can be promising antifungal candidates to treat cryptococcosis.
publishDate 2019
dc.date.issued.fl_str_mv 2019
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