Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity

Autores
Laali, Kenneth K.; Greves, William J.; Zwarycz, Angela T.; Correa-Smits, Sebastian J.; Troendle, Frederick J.; Borosky, Gabriela Leonor; Akhtar, Sharoon; Manna, Alak; Paulus, Aneel; Chanan-Khan, Asher; Nukaya, Manabu; Kennedy, Gregory D.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).
Fil: Laali, Kenneth K.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Greves, William J.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Zwarycz, Angela T.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Correa-Smits, Sebastian J.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Troendle, Frederick J.. University of North Florida. Department of Chemistry; 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: Akhtar, Sharoon. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Paulus, Aneel. Mayo Clinic. Department of Hematology and Oncology ; Estados Unidos
Fil: Chanan-Khan, Asher. Mayo Clinic. Department of Hematology and Oncology ; Estados Unidos
Fil: Nukaya, Manabu. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Kennedy, Gregory D.. University of North Florida. Department of Chemistry; Estados Unidos
Materia
ANTITUMOR AGENTS
APOPTOSIS
BINDING AFFINITY
CURCUMINOIDS
MULTIPLE MYELOMA
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:11336/85715
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/85715
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activityLaali, Kenneth K.Greves, William J.Zwarycz, Angela T.Correa-Smits, Sebastian J.Troendle, Frederick J.Borosky, Gabriela LeonorAkhtar, SharoonManna, AlakPaulus, AneelChanan-Khan, AsherNukaya, ManabuKennedy, Gregory D.ANTITUMOR AGENTSAPOPTOSISBINDING AFFINITYCURCUMINOIDSMULTIPLE MYELOMAhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).Fil: Laali, Kenneth K.. University of North Florida. Department of Chemistry; Estados UnidosFil: Greves, William J.. University of North Florida. Department of Chemistry; Estados UnidosFil: Zwarycz, Angela T.. University of North Florida. Department of Chemistry; Estados UnidosFil: Correa-Smits, Sebastian J.. University of North Florida. Department of Chemistry; Estados UnidosFil: Troendle, Frederick J.. University of North Florida. Department of Chemistry; 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: Akhtar, Sharoon. Mayo Clinic. Department of Cancer Biology; Estados UnidosFil: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados UnidosFil: Paulus, Aneel. Mayo Clinic. Department of Hematology and Oncology ; Estados UnidosFil: Chanan-Khan, Asher. Mayo Clinic. Department of Hematology and Oncology ; Estados UnidosFil: Nukaya, Manabu. University of North Florida. Department of Chemistry; Estados UnidosFil: Kennedy, Gregory D.. University of North Florida. Department of Chemistry; Estados UnidosWiley VCH Verlag2018-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85715Laali, Kenneth K.; Greves, William J.; Zwarycz, Angela T.; Correa-Smits, Sebastian J.; Troendle, Frederick J.; et al.; Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity; Wiley VCH Verlag; Chemmedchem; 13; 18; 9-2018; 1895-19081860-71791860-7187CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/cmdc.201800320info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/cmdc.201800320info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:05:17Zoai:ri.conicet.gov.ar:11336/85715instacron: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:34982025-10-22 11:05:18.038CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
title Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
spellingShingle Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
Laali, Kenneth K.
ANTITUMOR AGENTS
APOPTOSIS
BINDING AFFINITY
CURCUMINOIDS
MULTIPLE MYELOMA
title_short Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
title_full Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
title_fullStr Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
title_full_unstemmed Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
title_sort Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity
dc.creator.none.fl_str_mv Laali, Kenneth K.
Greves, William J.
Zwarycz, Angela T.
Correa-Smits, Sebastian J.
Troendle, Frederick J.
Borosky, Gabriela Leonor
Akhtar, Sharoon
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
Nukaya, Manabu
Kennedy, Gregory D.
author Laali, Kenneth K.
author_facet Laali, Kenneth K.
Greves, William J.
Zwarycz, Angela T.
Correa-Smits, Sebastian J.
Troendle, Frederick J.
Borosky, Gabriela Leonor
Akhtar, Sharoon
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
Nukaya, Manabu
Kennedy, Gregory D.
author_role author
author2 Greves, William J.
Zwarycz, Angela T.
Correa-Smits, Sebastian J.
Troendle, Frederick J.
Borosky, Gabriela Leonor
Akhtar, Sharoon
Manna, Alak
Paulus, Aneel
Chanan-Khan, Asher
Nukaya, Manabu
Kennedy, Gregory D.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTITUMOR AGENTS
APOPTOSIS
BINDING AFFINITY
CURCUMINOIDS
MULTIPLE MYELOMA
topic ANTITUMOR AGENTS
APOPTOSIS
BINDING AFFINITY
CURCUMINOIDS
MULTIPLE MYELOMA
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) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).
Fil: Laali, Kenneth K.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Greves, William J.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Zwarycz, Angela T.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Correa-Smits, Sebastian J.. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Troendle, Frederick J.. University of North Florida. Department of Chemistry; 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: Akhtar, Sharoon. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Manna, Alak. Mayo Clinic. Department of Cancer Biology; Estados Unidos
Fil: Paulus, Aneel. Mayo Clinic. Department of Hematology and Oncology ; Estados Unidos
Fil: Chanan-Khan, Asher. Mayo Clinic. Department of Hematology and Oncology ; Estados Unidos
Fil: Nukaya, Manabu. University of North Florida. Department of Chemistry; Estados Unidos
Fil: Kennedy, Gregory D.. University of North Florida. Department of Chemistry; Estados Unidos
description In a continuing search for curcuminoid (CUR) compounds with antitumor activity, a novel series of heterocyclic CUR–BF2 adducts and CUR compounds based on indole, benzothiophene, and benzofuran along with their aryl pyrazoles were synthesized. Computational docking studies were performed to compare binding efficiency to target proteins involved in specific cancers, namely HER2, proteasome, VEGFR, BRAF, and Bcl-2, versus known inhibitor drugs. The majority presented very good binding affinities, similar to, and even more favorable than those of known inhibitors. The indole-based CUR–BF2 and CUR compounds and their bis-thiocyanato derivatives exhibited high anti-proliferative and apoptotic activity by in vitro bioassays against a panel of 60 cancer cell lines, more specifically against multiple myeloma (MM) cell lines (KMS11, MM1.S, and RPMI-8226) with significantly lower IC50 values versus healthy PBMC cells; they also exhibited higher anti-proliferative activity in human colorectal cancer cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) than the parent curcumin, while showing notably lower cytotoxicity in normal colon cells (CCD112CoN and CCD841CoN).
publishDate 2018
dc.date.none.fl_str_mv 2018-09
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/11336/85715
Laali, Kenneth K.; Greves, William J.; Zwarycz, Angela T.; Correa-Smits, Sebastian J.; Troendle, Frederick J.; et al.; Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity; Wiley VCH Verlag; Chemmedchem; 13; 18; 9-2018; 1895-1908
1860-7179
1860-7187
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85715
identifier_str_mv Laali, Kenneth K.; Greves, William J.; Zwarycz, Angela T.; Correa-Smits, Sebastian J.; Troendle, Frederick J.; et al.; Synthesis, computational docking study, and biological evaluation of a library of heterocyclic curcuminoids with remarkable antitumor activity; Wiley VCH Verlag; Chemmedchem; 13; 18; 9-2018; 1895-1908
1860-7179
1860-7187
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/cmdc.201800320
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/cmdc.201800320
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 Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
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 12.982451

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