Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors

Autores
Dutta Guptan, Sayan; Bommaka, Manish Kumar; Mazaira, Gisela Ileana; Galigniana, Mario Daniel; Subrahmanyam, Chavali Venkata Satya; Gowrishankar, Naryanasamy Lachmana; Raghavendra, Nulgumnalli Manjunathaiah
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The ubiquitously expressed heat shock protein 90 is an encouraging target for the development of novel anticancer agents. In a program directed towards uncovering novel chemical scaffolds against Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designing software by including the required conserved water molecules. The results of the docking studies predicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxy acetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6) and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. The synthesized Mannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by the colorimetric Malachite green assay. Subsequently, the molecules were screened for their antiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activity profile of the identified derivatives correlated well with their docking results.
Fil: Dutta Guptan, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; India
Fil: Bommaka, Manish Kumar. Osmania University; India
Fil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Subrahmanyam, Chavali Venkata Satya. Osmania University; India
Fil: Gowrishankar, Naryanasamy Lachmana. Swami Vivekananda Institute of Pharmaceutical Sciences; India
Fil: Raghavendra, Nulgumnalli Manjunathaiah. Osmania University; India
Materia
Docking
Hsp90
Mannich Base
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:11336/49461
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/49461
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitorsDutta Guptan, SayanBommaka, Manish KumarMazaira, Gisela IleanaGaligniana, Mario DanielSubrahmanyam, Chavali Venkata SatyaGowrishankar, Naryanasamy LachmanaRaghavendra, Nulgumnalli ManjunathaiahDockingHsp90Mannich Basehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The ubiquitously expressed heat shock protein 90 is an encouraging target for the development of novel anticancer agents. In a program directed towards uncovering novel chemical scaffolds against Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designing software by including the required conserved water molecules. The results of the docking studies predicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxy acetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6) and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. The synthesized Mannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by the colorimetric Malachite green assay. Subsequently, the molecules were screened for their antiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activity profile of the identified derivatives correlated well with their docking results.Fil: Dutta Guptan, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; IndiaFil: Bommaka, Manish Kumar. Osmania University; IndiaFil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Subrahmanyam, Chavali Venkata Satya. Osmania University; IndiaFil: Gowrishankar, Naryanasamy Lachmana. Swami Vivekananda Institute of Pharmaceutical Sciences; IndiaFil: Raghavendra, Nulgumnalli Manjunathaiah. Osmania University; IndiaElsevier Science2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/49461Dutta Guptan, Sayan; Bommaka, Manish Kumar; Mazaira, Gisela Ileana; Galigniana, Mario Daniel; Subrahmanyam, Chavali Venkata Satya; et al.; Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors; Elsevier Science; International Journal of Biological Macromolecules; 80; 7-2015; 253-2590141-81301879-0003CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ijbiomac.2015.06.039info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0141813015004420?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 Técnicas2025-09-29T10:45:56Zoai:ri.conicet.gov.ar:11336/49461instacron: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:34982025-09-29 10:45:57.051CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
title Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
spellingShingle Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
Dutta Guptan, Sayan
Docking
Hsp90
Mannich Base
title_short Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
title_full Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
title_fullStr Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
title_full_unstemmed Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
title_sort Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors
dc.creator.none.fl_str_mv Dutta Guptan, Sayan
Bommaka, Manish Kumar
Mazaira, Gisela Ileana
Galigniana, Mario Daniel
Subrahmanyam, Chavali Venkata Satya
Gowrishankar, Naryanasamy Lachmana
Raghavendra, Nulgumnalli Manjunathaiah
author Dutta Guptan, Sayan
author_facet Dutta Guptan, Sayan
Bommaka, Manish Kumar
Mazaira, Gisela Ileana
Galigniana, Mario Daniel
Subrahmanyam, Chavali Venkata Satya
Gowrishankar, Naryanasamy Lachmana
Raghavendra, Nulgumnalli Manjunathaiah
author_role author
author2 Bommaka, Manish Kumar
Mazaira, Gisela Ileana
Galigniana, Mario Daniel
Subrahmanyam, Chavali Venkata Satya
Gowrishankar, Naryanasamy Lachmana
Raghavendra, Nulgumnalli Manjunathaiah
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Docking
Hsp90
Mannich Base
topic Docking
Hsp90
Mannich Base
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The ubiquitously expressed heat shock protein 90 is an encouraging target for the development of novel anticancer agents. In a program directed towards uncovering novel chemical scaffolds against Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designing software by including the required conserved water molecules. The results of the docking studies predicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxy acetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6) and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. The synthesized Mannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by the colorimetric Malachite green assay. Subsequently, the molecules were screened for their antiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activity profile of the identified derivatives correlated well with their docking results.
Fil: Dutta Guptan, Sayan. Osmania University; India. Jawaharlal Nehru Technological University; India
Fil: Bommaka, Manish Kumar. Osmania University; India
Fil: Mazaira, Gisela Ileana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Subrahmanyam, Chavali Venkata Satya. Osmania University; India
Fil: Gowrishankar, Naryanasamy Lachmana. Swami Vivekananda Institute of Pharmaceutical Sciences; India
Fil: Raghavendra, Nulgumnalli Manjunathaiah. Osmania University; India
description The ubiquitously expressed heat shock protein 90 is an encouraging target for the development of novel anticancer agents. In a program directed towards uncovering novel chemical scaffolds against Hsp90, we performed molecular docking studies using Tripos-Sybyl drug designing software by including the required conserved water molecules. The results of the docking studies predicted Mannich bases derived from 2,4-dihydroxy acetophenone/5-chloro 2,4-dihydroxy acetophenone as potential Hsp90 inhibitors. Subsequently, a few of them were synthesized (1-6) and characterized by IR, 1H NMR, 13C NMR and mass spectral analysis. The synthesized Mannich compounds were evaluated for their potential to suppress Hsp90 ATPase activity by the colorimetric Malachite green assay. Subsequently, the molecules were screened for their antiproilferative effect against PC3 pancreatic carcinoma cells by adopting the 3-(4,5-dimethythiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay method. The activity profile of the identified derivatives correlated well with their docking results.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
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/11336/49461
Dutta Guptan, Sayan; Bommaka, Manish Kumar; Mazaira, Gisela Ileana; Galigniana, Mario Daniel; Subrahmanyam, Chavali Venkata Satya; et al.; Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors; Elsevier Science; International Journal of Biological Macromolecules; 80; 7-2015; 253-259
0141-8130
1879-0003
CONICET Digital
CONICET
url http://hdl.handle.net/11336/49461
identifier_str_mv Dutta Guptan, Sayan; Bommaka, Manish Kumar; Mazaira, Gisela Ileana; Galigniana, Mario Daniel; Subrahmanyam, Chavali Venkata Satya; et al.; Molecular docking study, synthesis and biological evaluation of Mannich bases as Hsp90 inhibitors; Elsevier Science; International Journal of Biological Macromolecules; 80; 7-2015; 253-259
0141-8130
1879-0003
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.ijbiomac.2015.06.039
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0141813015004420?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
publisher.none.fl_str_mv Elsevier Science
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 13.070432

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