Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay

Autores
Laali, Kenneth K.; Greves, William J.; Correa-Smits, Sebastian J.; Zwarycz, Angela T.; Bunge, Scott D.; Borosky, Gabriela Leonor; Manna, Alak; Paulus, Aneel; Chanan-Khan, Asher
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In a continuing search for “curcuminoid (CUR) inspired” compounds with potential antitumor activity, a series of 21 new CUR-BF2 adducts and CURs bearing fluorine, trifluoromethylthio, trifluoromethoxy, and trifluoromethyl substitutents were synthesized in an effort to improve physicochemical properties such as lipophilicity and metabolic stability. Bulky activating groups namely methoxy, acetoxy, and benzyloxy groups were introduced as a way to tune steric/electronic effects. Multinuclear NMR, X-ray analysis and DFT optimizations confirmed that despite significant differences in their substitution patterns these curcuminoids all exist as enolic tautomers, and their CUR-BF2 adducts are symmetrical with equal B-O bond distances. To gauge the potential role of the enolic moiety in interaction with proteins, a library consisting of 22 aryl-pyrazole and isoxazole derivatives were synthesized. 19F NMR provided a rapid and convenient assay to monitor these transformations. Computational/docking studies were performed to compare binding efficiency to target proteins involved in specific cancers versus known inhibitor drugs. Several CUR pyrazoles and isoxazoles presented very favorable binding affinities, particularly those bearing CF3 groups. Highly favorable docking affinities were observed for the benzyloxy-substituted CURs. Selected compounds were tested by in-vitro bioassay against a panel of 60 cancer cell lines, and more specifically against leukemia cell lines by cell viability assay.
Fil: Laali, Kenneth K.. University Of North Florida; Estados Unidos
Fil: Greves, William J.. University Of North Florida; Estados Unidos
Fil: Correa-Smits, Sebastian J.. University Of North Florida; Estados Unidos
Fil: Zwarycz, Angela T.. University Of North Florida; Estados Unidos
Fil: Bunge, Scott D.. Kent State University; Estados Unidos
Fil: Borosky, Gabriela Leonor. 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: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Paulus, Aneel. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Chanan-Khan, Asher. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Materia
COMPUTATIONAL DOCKING
CURCUMINOID-BF2 ADDUCTS
FLUORINATED CUR-PYRAZOLES AND ISOXAZOLES
FLUOROCURCUMINOIDS
IN-VITRO BIOASSAY
X-RAY ANALYSIS
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:11336/86170
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/86170
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassayLaali, Kenneth K.Greves, William J.Correa-Smits, Sebastian J.Zwarycz, Angela T.Bunge, Scott D.Borosky, Gabriela LeonorManna, AlakPaulus, AneelChanan-Khan, AsherCOMPUTATIONAL DOCKINGCURCUMINOID-BF2 ADDUCTSFLUORINATED CUR-PYRAZOLES AND ISOXAZOLESFLUOROCURCUMINOIDSIN-VITRO BIOASSAYX-RAY ANALYSIShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In a continuing search for “curcuminoid (CUR) inspired” compounds with potential antitumor activity, a series of 21 new CUR-BF2 adducts and CURs bearing fluorine, trifluoromethylthio, trifluoromethoxy, and trifluoromethyl substitutents were synthesized in an effort to improve physicochemical properties such as lipophilicity and metabolic stability. Bulky activating groups namely methoxy, acetoxy, and benzyloxy groups were introduced as a way to tune steric/electronic effects. Multinuclear NMR, X-ray analysis and DFT optimizations confirmed that despite significant differences in their substitution patterns these curcuminoids all exist as enolic tautomers, and their CUR-BF2 adducts are symmetrical with equal B-O bond distances. To gauge the potential role of the enolic moiety in interaction with proteins, a library consisting of 22 aryl-pyrazole and isoxazole derivatives were synthesized. 19F NMR provided a rapid and convenient assay to monitor these transformations. Computational/docking studies were performed to compare binding efficiency to target proteins involved in specific cancers versus known inhibitor drugs. Several CUR pyrazoles and isoxazoles presented very favorable binding affinities, particularly those bearing CF3 groups. Highly favorable docking affinities were observed for the benzyloxy-substituted CURs. Selected compounds were tested by in-vitro bioassay against a panel of 60 cancer cell lines, and more specifically against leukemia cell lines by cell viability assay.Fil: Laali, Kenneth K.. University Of North Florida; Estados UnidosFil: Greves, William J.. University Of North Florida; Estados UnidosFil: Correa-Smits, Sebastian J.. University Of North Florida; Estados UnidosFil: Zwarycz, Angela T.. University Of North Florida; Estados UnidosFil: Bunge, Scott D.. Kent State University; Estados UnidosFil: Borosky, Gabriela Leonor. 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: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados UnidosFil: Paulus, Aneel. Mayo Clinic. Department of Cancer Biology; Estados UnidosFil: Chanan-Khan, Asher. Mayo Clinic. Department of Cancer Biology; Estados UnidosElsevier Science Sa2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86170Laali, Kenneth K.; Greves, William J.; Correa-Smits, Sebastian J.; Zwarycz, Angela T.; Bunge, Scott D.; et al.; Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay; Elsevier Science Sa; Journal of Fluorine Chemistry; 206; 2-2018; 82-980022-1139CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jfluchem.2017.11.013info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022113917303871?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:22:10Zoai:ri.conicet.gov.ar:11336/86170instacron: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:34982025-10-15 14:22:10.53CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
title Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
spellingShingle Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
Laali, Kenneth K.
COMPUTATIONAL DOCKING
CURCUMINOID-BF2 ADDUCTS
FLUORINATED CUR-PYRAZOLES AND ISOXAZOLES
FLUOROCURCUMINOIDS
IN-VITRO BIOASSAY
X-RAY ANALYSIS
title_short Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
title_full Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
title_fullStr Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
title_full_unstemmed Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
title_sort Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay
dc.creator.none.fl_str_mv Laali, Kenneth K.
Greves, William J.
Correa-Smits, Sebastian J.
Zwarycz, Angela T.
Bunge, Scott D.
Borosky, Gabriela Leonor
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
author Laali, Kenneth K.
author_facet Laali, Kenneth K.
Greves, William J.
Correa-Smits, Sebastian J.
Zwarycz, Angela T.
Bunge, Scott D.
Borosky, Gabriela Leonor
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
author_role author
author2 Greves, William J.
Correa-Smits, Sebastian J.
Zwarycz, Angela T.
Bunge, Scott D.
Borosky, Gabriela Leonor
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv COMPUTATIONAL DOCKING
CURCUMINOID-BF2 ADDUCTS
FLUORINATED CUR-PYRAZOLES AND ISOXAZOLES
FLUOROCURCUMINOIDS
IN-VITRO BIOASSAY
X-RAY ANALYSIS
topic COMPUTATIONAL DOCKING
CURCUMINOID-BF2 ADDUCTS
FLUORINATED CUR-PYRAZOLES AND ISOXAZOLES
FLUOROCURCUMINOIDS
IN-VITRO BIOASSAY
X-RAY ANALYSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In a continuing search for “curcuminoid (CUR) inspired” compounds with potential antitumor activity, a series of 21 new CUR-BF2 adducts and CURs bearing fluorine, trifluoromethylthio, trifluoromethoxy, and trifluoromethyl substitutents were synthesized in an effort to improve physicochemical properties such as lipophilicity and metabolic stability. Bulky activating groups namely methoxy, acetoxy, and benzyloxy groups were introduced as a way to tune steric/electronic effects. Multinuclear NMR, X-ray analysis and DFT optimizations confirmed that despite significant differences in their substitution patterns these curcuminoids all exist as enolic tautomers, and their CUR-BF2 adducts are symmetrical with equal B-O bond distances. To gauge the potential role of the enolic moiety in interaction with proteins, a library consisting of 22 aryl-pyrazole and isoxazole derivatives were synthesized. 19F NMR provided a rapid and convenient assay to monitor these transformations. Computational/docking studies were performed to compare binding efficiency to target proteins involved in specific cancers versus known inhibitor drugs. Several CUR pyrazoles and isoxazoles presented very favorable binding affinities, particularly those bearing CF3 groups. Highly favorable docking affinities were observed for the benzyloxy-substituted CURs. Selected compounds were tested by in-vitro bioassay against a panel of 60 cancer cell lines, and more specifically against leukemia cell lines by cell viability assay.
Fil: Laali, Kenneth K.. University Of North Florida; Estados Unidos
Fil: Greves, William J.. University Of North Florida; Estados Unidos
Fil: Correa-Smits, Sebastian J.. University Of North Florida; Estados Unidos
Fil: Zwarycz, Angela T.. University Of North Florida; Estados Unidos
Fil: Bunge, Scott D.. Kent State University; Estados Unidos
Fil: Borosky, Gabriela Leonor. 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: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Paulus, Aneel. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Chanan-Khan, Asher. Mayo Clinic. Department of Cancer Biology; Estados Unidos
description In a continuing search for “curcuminoid (CUR) inspired” compounds with potential antitumor activity, a series of 21 new CUR-BF2 adducts and CURs bearing fluorine, trifluoromethylthio, trifluoromethoxy, and trifluoromethyl substitutents were synthesized in an effort to improve physicochemical properties such as lipophilicity and metabolic stability. Bulky activating groups namely methoxy, acetoxy, and benzyloxy groups were introduced as a way to tune steric/electronic effects. Multinuclear NMR, X-ray analysis and DFT optimizations confirmed that despite significant differences in their substitution patterns these curcuminoids all exist as enolic tautomers, and their CUR-BF2 adducts are symmetrical with equal B-O bond distances. To gauge the potential role of the enolic moiety in interaction with proteins, a library consisting of 22 aryl-pyrazole and isoxazole derivatives were synthesized. 19F NMR provided a rapid and convenient assay to monitor these transformations. Computational/docking studies were performed to compare binding efficiency to target proteins involved in specific cancers versus known inhibitor drugs. Several CUR pyrazoles and isoxazoles presented very favorable binding affinities, particularly those bearing CF3 groups. Highly favorable docking affinities were observed for the benzyloxy-substituted CURs. Selected compounds were tested by in-vitro bioassay against a panel of 60 cancer cell lines, and more specifically against leukemia cell lines by cell viability assay.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
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/11336/86170
Laali, Kenneth K.; Greves, William J.; Correa-Smits, Sebastian J.; Zwarycz, Angela T.; Bunge, Scott D.; et al.; Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay; Elsevier Science Sa; Journal of Fluorine Chemistry; 206; 2-2018; 82-98
0022-1139
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86170
identifier_str_mv Laali, Kenneth K.; Greves, William J.; Correa-Smits, Sebastian J.; Zwarycz, Angela T.; Bunge, Scott D.; et al.; Novel fluorinated curcuminoids and their pyrazole and isoxazole derivatives: Synthesis, structural studies, Computational/Docking and in-vitro bioassay; Elsevier Science Sa; Journal of Fluorine Chemistry; 206; 2-2018; 82-98
0022-1139
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jfluchem.2017.11.013
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0022113917303871?via%3Dihub
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
dc.publisher.none.fl_str_mv Elsevier Science Sa
publisher.none.fl_str_mv Elsevier Science Sa
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 13.22299

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