Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.bmc.2018.10.032 http://hdl.handle.net/11449/185101 |
Resumo: | Leishmaniasis is one of the most important neglected tropical diseases (NTDs) that are especially common among low-income populations in developing regions of Africa, Asia, and the Americas. Many natural products, particularly alkaloids, have been reported to have inhibitory activity against arginase, the key enzyme in the pathology caused by Leishmania sp. In this way, piperidine alkaloids (-)-cassine (1), (-)-spectaline (2), (-)-3-O-acetylcassine (3), and (-)-3-O-acetylspectaline (4) were isolated from Senna spectabilis flowers. These compounds (1/2 and 3/4) initially present as homologous mixtures were separated by high performance liquid chromatography and evaluated against the promastigote phase of Leishmania amazonensis. In addition, molecular docking simulations were implemented in order to probe the binding modes of the ligands 1-4 to the amino acids in the active site of L. amazonensis arginase. Alkaloid 2 (IC50 15.81 mu g mL(-1)) was the most effective against L. amazonensis. Compounds 2 and 4, with larger side chain, were more effective against the parasite than compounds 1 and 3. The cell viability test on Vero cells revealed that compound 2 (CC50 66.67 mu g mL-1) was the most toxic. The acetyl group in the 3-O position of the parent structures reduced the leishmanicidal activity and the toxicity of the alkaloids. Further, molecular docking suggested that Asn143 is essential for arginase to interact with (-)-spectaline-derived compounds, which agreed with the IC50 measurements. Our findings revealed that S. spectabilis is an important source of piperidine alkaloids with leishmanicidal activity. Moreover, the natural compound 3 has been isolated for the first time. Experimental investigation combined with theoretical study advances knowledge about the enzyme binding site mode of interaction and contributes to the design of new bioactive drugs against Leishmania infection. |
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Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilisFabaceaeSenna spectabilisPiperidine alkaloids(-)-Cassine(-)-SpectalineLeishmanicidal activityLeishmaniasis is one of the most important neglected tropical diseases (NTDs) that are especially common among low-income populations in developing regions of Africa, Asia, and the Americas. Many natural products, particularly alkaloids, have been reported to have inhibitory activity against arginase, the key enzyme in the pathology caused by Leishmania sp. In this way, piperidine alkaloids (-)-cassine (1), (-)-spectaline (2), (-)-3-O-acetylcassine (3), and (-)-3-O-acetylspectaline (4) were isolated from Senna spectabilis flowers. These compounds (1/2 and 3/4) initially present as homologous mixtures were separated by high performance liquid chromatography and evaluated against the promastigote phase of Leishmania amazonensis. In addition, molecular docking simulations were implemented in order to probe the binding modes of the ligands 1-4 to the amino acids in the active site of L. amazonensis arginase. Alkaloid 2 (IC50 15.81 mu g mL(-1)) was the most effective against L. amazonensis. Compounds 2 and 4, with larger side chain, were more effective against the parasite than compounds 1 and 3. The cell viability test on Vero cells revealed that compound 2 (CC50 66.67 mu g mL-1) was the most toxic. The acetyl group in the 3-O position of the parent structures reduced the leishmanicidal activity and the toxicity of the alkaloids. Further, molecular docking suggested that Asn143 is essential for arginase to interact with (-)-spectaline-derived compounds, which agreed with the IC50 measurements. Our findings revealed that S. spectabilis is an important source of piperidine alkaloids with leishmanicidal activity. Moreover, the natural compound 3 has been isolated for the first time. Experimental investigation combined with theoretical study advances knowledge about the enzyme binding site mode of interaction and contributes to the design of new bioactive drugs against Leishmania infection.Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Uberlandia, Inst Quim, Nucleo Pesquisa Prod Nat NuPPeN, BR-38400902 Uberlandia, MG, BrazilUniv Fed Uberlandia, Inst Ciencias Biomed, BR-38400902 Uberlandia, MG, BrazilUniv Fed Triangulo Mineiro, Inst Ciencias Exatas Nat & Educ, Dept Fis, Lab Biofis Teor, BR-38064200 Uberaba, MG, BrazilUniv Fed Alfenas, Inst Quim, Lab Pesquisa Quim Med PeQuiM, BR-37133840 Alfenas, MG, BrazilUniv Estadual Paulista, Inst Quim, Dept Quim Organ, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, POB 355, BR-14801970 Araraquara, SP, BrazilUniv Fed Triangulo Mineiro, Inst Ciencias Exatas Nat & Educ, Dept Quim, Nucleo Desenvolvimento Compostos Bioativos NDCBio, BR-38064200 Uberaba, MG, BrazilUniv Estadual Paulista, Inst Quim, Dept Quim Organ, Nucleo Bioensaios Biossintese & Ecofisiol Prod Na, POB 355, BR-14801970 Araraquara, SP, BrazilFAPEMIG: APQ-02481-14CNPq: 449846/2014-8FAPEMIG: REDE-113/10FAPEMIG: CEX-RED-00010-14Elsevier B.V.Universidade Federal de Uberlândia (UFU)Univ Fed Triangulo MineiroUniv Fed AlfenasUniversidade Estadual Paulista (Unesp)Moreira Lacerda, Rosimeire BorgesFreitas, Thamires RodriguesMartins, Mario MachadoTeixeira, Thaise LaraSilva, Claudio Vieira daCandido, Pamela AparecidaOliveira, Ronaldo Junio deViegas Junior, ClaudioBolzani, Vanderlan da Silva [UNESP]Danuello, AmandaPivatto, Marcos2019-10-04T12:32:41Z2019-10-04T12:32:41Z2018-12-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5816-5823http://dx.doi.org/10.1016/j.bmc.2018.10.032Bioorganic & Medicinal Chemistry. Oxford: Pergamon-elsevier Science Ltd, v. 26, n. 22, p. 5816-5823, 2018.0968-0896http://hdl.handle.net/11449/18510110.1016/j.bmc.2018.10.032WOS:000451196900006Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBioorganic & Medicinal Chemistryinfo:eu-repo/semantics/openAccess2021-10-23T19:02:05Zoai:repositorio.unesp.br:11449/185101Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T19:02:05Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
title |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
spellingShingle |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis Moreira Lacerda, Rosimeire Borges Fabaceae Senna spectabilis Piperidine alkaloids (-)-Cassine (-)-Spectaline Leishmanicidal activity |
title_short |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
title_full |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
title_fullStr |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
title_full_unstemmed |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
title_sort |
Isolation, leishmanicidal evaluation and molecular docking simulations of piperidine alkaloids from Senna spectabilis |
author |
Moreira Lacerda, Rosimeire Borges |
author_facet |
Moreira Lacerda, Rosimeire Borges Freitas, Thamires Rodrigues Martins, Mario Machado Teixeira, Thaise Lara Silva, Claudio Vieira da Candido, Pamela Aparecida Oliveira, Ronaldo Junio de Viegas Junior, Claudio Bolzani, Vanderlan da Silva [UNESP] Danuello, Amanda Pivatto, Marcos |
author_role |
author |
author2 |
Freitas, Thamires Rodrigues Martins, Mario Machado Teixeira, Thaise Lara Silva, Claudio Vieira da Candido, Pamela Aparecida Oliveira, Ronaldo Junio de Viegas Junior, Claudio Bolzani, Vanderlan da Silva [UNESP] Danuello, Amanda Pivatto, Marcos |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Uberlândia (UFU) Univ Fed Triangulo Mineiro Univ Fed Alfenas Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Moreira Lacerda, Rosimeire Borges Freitas, Thamires Rodrigues Martins, Mario Machado Teixeira, Thaise Lara Silva, Claudio Vieira da Candido, Pamela Aparecida Oliveira, Ronaldo Junio de Viegas Junior, Claudio Bolzani, Vanderlan da Silva [UNESP] Danuello, Amanda Pivatto, Marcos |
dc.subject.por.fl_str_mv |
Fabaceae Senna spectabilis Piperidine alkaloids (-)-Cassine (-)-Spectaline Leishmanicidal activity |
topic |
Fabaceae Senna spectabilis Piperidine alkaloids (-)-Cassine (-)-Spectaline Leishmanicidal activity |
description |
Leishmaniasis is one of the most important neglected tropical diseases (NTDs) that are especially common among low-income populations in developing regions of Africa, Asia, and the Americas. Many natural products, particularly alkaloids, have been reported to have inhibitory activity against arginase, the key enzyme in the pathology caused by Leishmania sp. In this way, piperidine alkaloids (-)-cassine (1), (-)-spectaline (2), (-)-3-O-acetylcassine (3), and (-)-3-O-acetylspectaline (4) were isolated from Senna spectabilis flowers. These compounds (1/2 and 3/4) initially present as homologous mixtures were separated by high performance liquid chromatography and evaluated against the promastigote phase of Leishmania amazonensis. In addition, molecular docking simulations were implemented in order to probe the binding modes of the ligands 1-4 to the amino acids in the active site of L. amazonensis arginase. Alkaloid 2 (IC50 15.81 mu g mL(-1)) was the most effective against L. amazonensis. Compounds 2 and 4, with larger side chain, were more effective against the parasite than compounds 1 and 3. The cell viability test on Vero cells revealed that compound 2 (CC50 66.67 mu g mL-1) was the most toxic. The acetyl group in the 3-O position of the parent structures reduced the leishmanicidal activity and the toxicity of the alkaloids. Further, molecular docking suggested that Asn143 is essential for arginase to interact with (-)-spectaline-derived compounds, which agreed with the IC50 measurements. Our findings revealed that S. spectabilis is an important source of piperidine alkaloids with leishmanicidal activity. Moreover, the natural compound 3 has been isolated for the first time. Experimental investigation combined with theoretical study advances knowledge about the enzyme binding site mode of interaction and contributes to the design of new bioactive drugs against Leishmania infection. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-01 2019-10-04T12:32:41Z 2019-10-04T12:32:41Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.bmc.2018.10.032 Bioorganic & Medicinal Chemistry. Oxford: Pergamon-elsevier Science Ltd, v. 26, n. 22, p. 5816-5823, 2018. 0968-0896 http://hdl.handle.net/11449/185101 10.1016/j.bmc.2018.10.032 WOS:000451196900006 |
url |
http://dx.doi.org/10.1016/j.bmc.2018.10.032 http://hdl.handle.net/11449/185101 |
identifier_str_mv |
Bioorganic & Medicinal Chemistry. Oxford: Pergamon-elsevier Science Ltd, v. 26, n. 22, p. 5816-5823, 2018. 0968-0896 10.1016/j.bmc.2018.10.032 WOS:000451196900006 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bioorganic & Medicinal Chemistry |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
5816-5823 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1797789774639005696 |