Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10198/18590 |
Resumo: | A series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC50 = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC50 = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI50 = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI50 = 200 ± 2.8 μM) and 3b (GI50 = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC50 values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC50 = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket. |
id |
RCAP_2d49bfe21ab2a8d4f0f79d5c369b192a |
---|---|
oai_identifier_str |
oai:bibliotecadigital.ipb.pt:10198/18590 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studiesAcute toxicityAntimicrobial activityAntioxidant activityCytotoxicityEnantiopure isoxazolidinesMolecular dockingα-Amylase inhibitionA series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC50 = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC50 = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI50 = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI50 = 200 ± 2.8 μM) and 3b (GI50 = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC50 values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC50 = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket.Biblioteca Digital do IPBMosbah, HabibChahdoura, HassibaMannai, AsmaSnoussi, MejdiAouadi, KaïssAbreu, Rui M.V.Bouslama, AliAchour, LotfiSelmi, Boulbaba2018-01-19T10:00:00Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10198/18590engMosbah, Habib; Chahdoura, Hassiba; Mannai, Asma; Snoussi, Mejdi; Aouadi, Kaïss; Abreu, Rui M.V.; Bouslama, Ali; Achour, Lotfi; Selmi, Boulbaba (2019). Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies. Applied Biochemistry and Biotechnology. ISSN 0273-2289. 187:3, p. 1113–11300273-228910.1007/s12010-018-2868-2info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-21T10:42:44Zoai:bibliotecadigital.ipb.pt:10198/18590Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:08:55.076537Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
title |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
spellingShingle |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies Mosbah, Habib Acute toxicity Antimicrobial activity Antioxidant activity Cytotoxicity Enantiopure isoxazolidines Molecular docking α-Amylase inhibition |
title_short |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
title_full |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
title_fullStr |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
title_full_unstemmed |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
title_sort |
Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies |
author |
Mosbah, Habib |
author_facet |
Mosbah, Habib Chahdoura, Hassiba Mannai, Asma Snoussi, Mejdi Aouadi, Kaïss Abreu, Rui M.V. Bouslama, Ali Achour, Lotfi Selmi, Boulbaba |
author_role |
author |
author2 |
Chahdoura, Hassiba Mannai, Asma Snoussi, Mejdi Aouadi, Kaïss Abreu, Rui M.V. Bouslama, Ali Achour, Lotfi Selmi, Boulbaba |
author2_role |
author author author author author author author author |
dc.contributor.none.fl_str_mv |
Biblioteca Digital do IPB |
dc.contributor.author.fl_str_mv |
Mosbah, Habib Chahdoura, Hassiba Mannai, Asma Snoussi, Mejdi Aouadi, Kaïss Abreu, Rui M.V. Bouslama, Ali Achour, Lotfi Selmi, Boulbaba |
dc.subject.por.fl_str_mv |
Acute toxicity Antimicrobial activity Antioxidant activity Cytotoxicity Enantiopure isoxazolidines Molecular docking α-Amylase inhibition |
topic |
Acute toxicity Antimicrobial activity Antioxidant activity Cytotoxicity Enantiopure isoxazolidines Molecular docking α-Amylase inhibition |
description |
A series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC50 = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC50 = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI50 = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI50 = 200 ± 2.8 μM) and 3b (GI50 = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC50 values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC50 = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01-19T10:00:00Z 2019 2019-01-01T00:00:00Z |
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://hdl.handle.net/10198/18590 |
url |
http://hdl.handle.net/10198/18590 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mosbah, Habib; Chahdoura, Hassiba; Mannai, Asma; Snoussi, Mejdi; Aouadi, Kaïss; Abreu, Rui M.V.; Bouslama, Ali; Achour, Lotfi; Selmi, Boulbaba (2019). Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies. Applied Biochemistry and Biotechnology. ISSN 0273-2289. 187:3, p. 1113–1130 0273-2289 10.1007/s12010-018-2868-2 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
_version_ |
1799135348892106752 |