Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea
- Autores
- Velappan, Anand Babu; Charan Raja, Mamilla R.; Datta, Dhrubajyoti; Tsai, Yi Ting; Halloum, Iman; Wan, Baojie; Kremer, Laurent; Gramajo, Hugo Cesar; Franzblau, Scott G.; Kar Mahapatra, Santanu; Debnath, Joy
- Año de publicación
- 2016
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among the 39 synthesized molecules, compounds 46, 57, 58 and 86 showed MIC values ≤ 10 μg/ml against H37Rv and mc26030 strains. The best molecule with a methyl at ortho position of the first aromatic ring and prenyl group at the meta position of the second aromatic ring showed the MIC value of 5.2 μg/ml and 1 μg/ml against H37Rv and mc26030 respectively, with mammalian cytotoxicity of 163.4 μg/ml. The effective compounds showed selective inhibitory effect on mycolic acid (epoxy mycolate) biosynthesis in14C-radiolabelled assay. At the same time these molecules also executed their potent immunomodulatory activity by up-regulation of IFN-γ and IL-12 and down-regulation of IL-10.
Fil: Velappan, Anand Babu. Sastra University; India
Fil: Charan Raja, Mamilla R.. Sastra University; India
Fil: Datta, Dhrubajyoti. Indian Institute of Science Education and Research Pune; India
Fil: Tsai, Yi Ting. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Halloum, Iman. Université de Montpellier; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Wan, Baojie. University of Illinois; Estados Unidos
Fil: Kremer, Laurent. Université de Montpellier; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia
Fil: Gramajo, Hugo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Franzblau, Scott G.. University of Illinois; Estados Unidos
Fil: Kar Mahapatra, Santanu. Sastra University; India
Fil: Debnath, Joy. Sastra University; India - Materia
-
ANTIMYCOBACTERIAL ACTIVITY
CYTOKINES
CYTOTOXICITY
DIARYL UREA
MYCOLIC ACID
STRUCTURE-ACTIVITY RELATIONSHIP
TUBERCULOSIS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
.jpg)
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/52712
Ver los metadatos del registro completo
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Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl ureaVelappan, Anand BabuCharan Raja, Mamilla R.Datta, DhrubajyotiTsai, Yi TingHalloum, ImanWan, BaojieKremer, LaurentGramajo, Hugo CesarFranzblau, Scott G.Kar Mahapatra, SantanuDebnath, JoyANTIMYCOBACTERIAL ACTIVITYCYTOKINESCYTOTOXICITYDIARYL UREAMYCOLIC ACIDSTRUCTURE-ACTIVITY RELATIONSHIPTUBERCULOSIShttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among the 39 synthesized molecules, compounds 46, 57, 58 and 86 showed MIC values ≤ 10 μg/ml against H37Rv and mc26030 strains. The best molecule with a methyl at ortho position of the first aromatic ring and prenyl group at the meta position of the second aromatic ring showed the MIC value of 5.2 μg/ml and 1 μg/ml against H37Rv and mc26030 respectively, with mammalian cytotoxicity of 163.4 μg/ml. The effective compounds showed selective inhibitory effect on mycolic acid (epoxy mycolate) biosynthesis in14C-radiolabelled assay. At the same time these molecules also executed their potent immunomodulatory activity by up-regulation of IFN-γ and IL-12 and down-regulation of IL-10.Fil: Velappan, Anand Babu. Sastra University; IndiaFil: Charan Raja, Mamilla R.. Sastra University; IndiaFil: Datta, Dhrubajyoti. Indian Institute of Science Education and Research Pune; IndiaFil: Tsai, Yi Ting. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Halloum, Iman. Université de Montpellier; Francia. Centre National de la Recherche Scientifique; FranciaFil: Wan, Baojie. University of Illinois; Estados UnidosFil: Kremer, Laurent. Université de Montpellier; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; FranciaFil: Gramajo, Hugo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Franzblau, Scott G.. University of Illinois; Estados UnidosFil: Kar Mahapatra, Santanu. Sastra University; IndiaFil: Debnath, Joy. Sastra University; IndiaElsevier France-editions Scientifiques Medicales Elsevier2016-09info: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/11336/52712Velappan, Anand Babu; Charan Raja, Mamilla R.; Datta, Dhrubajyoti; Tsai, Yi Ting; Halloum, Iman; et al.; Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal of Medical Chemistry; 125; 9-2016; 825-8410223-5234CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2016.09.083info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0223523416308170info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:03:11Zoai:ri.conicet.gov.ar:11336/52712instacron: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 11:03:11.814CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
| dc.title.none.fl_str_mv |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| title |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| spellingShingle |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea Velappan, Anand Babu ANTIMYCOBACTERIAL ACTIVITY CYTOKINES CYTOTOXICITY DIARYL UREA MYCOLIC ACID STRUCTURE-ACTIVITY RELATIONSHIP TUBERCULOSIS |
| title_short |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| title_full |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| title_fullStr |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| title_full_unstemmed |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| title_sort |
Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea |
| dc.creator.none.fl_str_mv |
Velappan, Anand Babu Charan Raja, Mamilla R. Datta, Dhrubajyoti Tsai, Yi Ting Halloum, Iman Wan, Baojie Kremer, Laurent Gramajo, Hugo Cesar Franzblau, Scott G. Kar Mahapatra, Santanu Debnath, Joy |
| author |
Velappan, Anand Babu |
| author_facet |
Velappan, Anand Babu Charan Raja, Mamilla R. Datta, Dhrubajyoti Tsai, Yi Ting Halloum, Iman Wan, Baojie Kremer, Laurent Gramajo, Hugo Cesar Franzblau, Scott G. Kar Mahapatra, Santanu Debnath, Joy |
| author_role |
author |
| author2 |
Charan Raja, Mamilla R. Datta, Dhrubajyoti Tsai, Yi Ting Halloum, Iman Wan, Baojie Kremer, Laurent Gramajo, Hugo Cesar Franzblau, Scott G. Kar Mahapatra, Santanu Debnath, Joy |
| author2_role |
author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
ANTIMYCOBACTERIAL ACTIVITY CYTOKINES CYTOTOXICITY DIARYL UREA MYCOLIC ACID STRUCTURE-ACTIVITY RELATIONSHIP TUBERCULOSIS |
| topic |
ANTIMYCOBACTERIAL ACTIVITY CYTOKINES CYTOTOXICITY DIARYL UREA MYCOLIC ACID STRUCTURE-ACTIVITY RELATIONSHIP TUBERCULOSIS |
| purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 |
| dc.description.none.fl_txt_mv |
Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among the 39 synthesized molecules, compounds 46, 57, 58 and 86 showed MIC values ≤ 10 μg/ml against H37Rv and mc26030 strains. The best molecule with a methyl at ortho position of the first aromatic ring and prenyl group at the meta position of the second aromatic ring showed the MIC value of 5.2 μg/ml and 1 μg/ml against H37Rv and mc26030 respectively, with mammalian cytotoxicity of 163.4 μg/ml. The effective compounds showed selective inhibitory effect on mycolic acid (epoxy mycolate) biosynthesis in14C-radiolabelled assay. At the same time these molecules also executed their potent immunomodulatory activity by up-regulation of IFN-γ and IL-12 and down-regulation of IL-10. Fil: Velappan, Anand Babu. Sastra University; India Fil: Charan Raja, Mamilla R.. Sastra University; India Fil: Datta, Dhrubajyoti. Indian Institute of Science Education and Research Pune; India Fil: Tsai, Yi Ting. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Halloum, Iman. Université de Montpellier; Francia. Centre National de la Recherche Scientifique; Francia Fil: Wan, Baojie. University of Illinois; Estados Unidos Fil: Kremer, Laurent. Université de Montpellier; Francia. Inserm; Francia. Centre National de la Recherche Scientifique; Francia Fil: Gramajo, Hugo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina Fil: Franzblau, Scott G.. University of Illinois; Estados Unidos Fil: Kar Mahapatra, Santanu. Sastra University; India Fil: Debnath, Joy. Sastra University; India |
| description |
Tuberculosis is a major threat for mankind and the emergence of resistance strain of Mycobacterium tuberculosis (Mtb) against first line antibiotics makes it lethal for human civilization. In this study, we have synthesized different diaryl urea derivatives targeting the inhibition of mycolic acid biosynthesis. Among the 39 synthesized molecules, compounds 46, 57, 58 and 86 showed MIC values ≤ 10 μg/ml against H37Rv and mc26030 strains. The best molecule with a methyl at ortho position of the first aromatic ring and prenyl group at the meta position of the second aromatic ring showed the MIC value of 5.2 μg/ml and 1 μg/ml against H37Rv and mc26030 respectively, with mammalian cytotoxicity of 163.4 μg/ml. The effective compounds showed selective inhibitory effect on mycolic acid (epoxy mycolate) biosynthesis in14C-radiolabelled assay. At the same time these molecules also executed their potent immunomodulatory activity by up-regulation of IFN-γ and IL-12 and down-regulation of IL-10. |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016-09 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
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publishedVersion |
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http://hdl.handle.net/11336/52712 Velappan, Anand Babu; Charan Raja, Mamilla R.; Datta, Dhrubajyoti; Tsai, Yi Ting; Halloum, Iman; et al.; Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal of Medical Chemistry; 125; 9-2016; 825-841 0223-5234 CONICET Digital CONICET |
| url |
http://hdl.handle.net/11336/52712 |
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Velappan, Anand Babu; Charan Raja, Mamilla R.; Datta, Dhrubajyoti; Tsai, Yi Ting; Halloum, Iman; et al.; Attenuation of Mycobacterium species through direct and macrophage mediated pathway by unsymmetrical diaryl urea; Elsevier France-editions Scientifiques Medicales Elsevier; European Journal of Medical Chemistry; 125; 9-2016; 825-841 0223-5234 CONICET Digital CONICET |
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eng |
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eng |
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info:eu-repo/semantics/altIdentifier/doi/10.1016/j.ejmech.2016.09.083 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0223523416308170 |
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Elsevier France-editions Scientifiques Medicales Elsevier |
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Elsevier France-editions Scientifiques Medicales Elsevier |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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