SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group

Autores
Nieto, Marcelo J.; Pierini, Adriana Beatriz; Singh, Nidhi; McCurdy, Christopher R.; Manzo, Ruben Hilario; Mazzierie, María
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in antistaphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
Fil: Nieto, Marcelo J.. Southern Illinois University al Edwardsville; Estados Unidos
Fil: Pierini, Adriana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Singh, Nidhi. Mississippi State University.; Estados Unidos
Fil: McCurdy, Christopher R.. Mississippi State University.; Estados Unidos
Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Mazzierie, María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Materia
BENZENESULFONYL GROUP
CONFORMATIONAL ANALYSIS
FLUOROQUINOLONES
PHARMACOPHORE
QSAR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/114352
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/114352
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl groupNieto, Marcelo J.Pierini, Adriana BeatrizSingh, NidhiMcCurdy, Christopher R.Manzo, Ruben HilarioMazzierie, MaríaBENZENESULFONYL GROUPCONFORMATIONAL ANALYSISFLUOROQUINOLONESPHARMACOPHOREQSARhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in antistaphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.Fil: Nieto, Marcelo J.. Southern Illinois University al Edwardsville; Estados UnidosFil: Pierini, Adriana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Singh, Nidhi. Mississippi State University.; Estados UnidosFil: McCurdy, Christopher R.. Mississippi State University.; Estados UnidosFil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaFil: Mazzierie, María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; ArgentinaBentham Science Publishers2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/114352Nieto, Marcelo J.; Pierini, Adriana Beatriz; Singh, Nidhi; McCurdy, Christopher R.; Manzo, Ruben Hilario; et al.; SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group; Bentham Science Publishers; Medicinal Chemistry; 8; 3; 5-2012; 349-3601573-40641875-6638CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2174/157340612800786633info:eu-repo/semantics/altIdentifier/url/https://www.eurekaselect.com/98945/articleinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:18:49Zoai:ri.conicet.gov.ar:11336/114352instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:18:49.636CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
title SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
spellingShingle SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
Nieto, Marcelo J.
BENZENESULFONYL GROUP
CONFORMATIONAL ANALYSIS
FLUOROQUINOLONES
PHARMACOPHORE
QSAR
title_short SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
title_full SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
title_fullStr SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
title_full_unstemmed SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
title_sort SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group
dc.creator.none.fl_str_mv Nieto, Marcelo J.
Pierini, Adriana Beatriz
Singh, Nidhi
McCurdy, Christopher R.
Manzo, Ruben Hilario
Mazzierie, María
author Nieto, Marcelo J.
author_facet Nieto, Marcelo J.
Pierini, Adriana Beatriz
Singh, Nidhi
McCurdy, Christopher R.
Manzo, Ruben Hilario
Mazzierie, María
author_role author
author2 Pierini, Adriana Beatriz
Singh, Nidhi
McCurdy, Christopher R.
Manzo, Ruben Hilario
Mazzierie, María
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv BENZENESULFONYL GROUP
CONFORMATIONAL ANALYSIS
FLUOROQUINOLONES
PHARMACOPHORE
QSAR
topic BENZENESULFONYL GROUP
CONFORMATIONAL ANALYSIS
FLUOROQUINOLONES
PHARMACOPHORE
QSAR
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in antistaphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
Fil: Nieto, Marcelo J.. Southern Illinois University al Edwardsville; Estados Unidos
Fil: Pierini, Adriana Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina
Fil: Singh, Nidhi. Mississippi State University.; Estados Unidos
Fil: McCurdy, Christopher R.. Mississippi State University.; Estados Unidos
Fil: Manzo, Ruben Hilario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
Fil: Mazzierie, María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina
description When a benzenesulfonyl moiety (BS) was bound to the N-piperazinyl ring of antibacterial fluoroquinolones (AMFQs) norfloxacin (NOR) or ciprofloxacin (CIP), the resulting benzenesulfonyl-fluoroquinolone (BSFQs) analogs showed an improved in vitro activity against Gram-positive strains. A bioisosterical replacement of the sulfonyl group for a carbonyl group led to the benzenecarboxamide-fluoroquinolones (BCFQs) that showed a similar trend in the antibacterial activity and spectrum. The BSFQs and BCFQs are considered members of the "dual targeting" fluoroquinolones, targeting both DNA gyrase and topoisomerase IV. To disclose the real contribution of the BS/BC moiety in antistaphylococcal activity, a 3D-QSAR analysis that included calculation of theoretical molecular descriptors and pharmacophore generation was performed. Previous and present QSAR results have confirmed the positive influence on activity of small electron donating p-substituent on the BS or BC moiety. The generated phamacophore model showed that both phenyl and SO2/CO groups are involved in the interaction with receptor. We postulate that the enhanced potency of BSFQs against Staphylococcus aureus compared to CIP and NOR could be caused by the presence of the BS moiety that resulted in enhanced binding to DNA gyrase of Sa. Additionally, their greater ability to enter bacterial cells by diffusion and a reduced susceptibility to FQ-specific efflux pumps could also make a contribution.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/114352
Nieto, Marcelo J.; Pierini, Adriana Beatriz; Singh, Nidhi; McCurdy, Christopher R.; Manzo, Ruben Hilario; et al.; SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group; Bentham Science Publishers; Medicinal Chemistry; 8; 3; 5-2012; 349-360
1573-4064
1875-6638
CONICET Digital
CONICET
url http://hdl.handle.net/11336/114352
identifier_str_mv Nieto, Marcelo J.; Pierini, Adriana Beatriz; Singh, Nidhi; McCurdy, Christopher R.; Manzo, Ruben Hilario; et al.; SAR analysis of new dual targeting fluoroquinolones. Implications of the benzenesulfonyl group; Bentham Science Publishers; Medicinal Chemistry; 8; 3; 5-2012; 349-360
1573-4064
1875-6638
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2174/157340612800786633
info:eu-repo/semantics/altIdentifier/url/https://www.eurekaselect.com/98945/article
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Bentham Science Publishers
publisher.none.fl_str_mv Bentham Science Publishers
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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