Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigeni...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kowit Hengphasatporn, Benyapa Kaewmalai, Somruedee Jansongsaeng, Vishnu Nayak Badavath, Thanaphon Saelee, Thamonwan Chokmahasarn, Tanatorn Khotavivattana, Yasuteru Shigeta, Thanyada Rungrotmongkol, Siwaporn Boonyasuppayakorn
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	alkyne-tagged flavonoid dengue virus drug discovery alkyne-azide cycloaddition flavone target identification Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/9ef2328a0bef47d48ff89b7f6333eafa
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9ef2328a0bef47d48ff89b7f6333eafa
record_format	dspace
spelling	oai:doaj.org-article:9ef2328a0bef47d48ff89b7f6333eafa2021-11-25T18:28:47ZAlkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads10.3390/molecules262269671420-3049https://doaj.org/article/9ef2328a0bef47d48ff89b7f6333eafa2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6967https://doaj.org/toc/1420-3049A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC<sub>50</sub> of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC<sub>50</sub> of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.Kowit HengphasatpornBenyapa KaewmalaiSomruedee JansongsaengVishnu Nayak BadavathThanaphon SaeleeThamonwan ChokmahasarnTanatorn KhotavivattanaYasuteru ShigetaThanyada RungrotmongkolSiwaporn BoonyasuppayakornMDPI AGarticlealkyne-tagged flavonoiddengue virusdrug discoveryalkyne-azide cycloadditionflavonetarget identificationOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6967, p 6967 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alkyne-tagged flavonoid dengue virus drug discovery alkyne-azide cycloaddition flavone target identification Organic chemistry QD241-441
spellingShingle	alkyne-tagged flavonoid dengue virus drug discovery alkyne-azide cycloaddition flavone target identification Organic chemistry QD241-441 Kowit Hengphasatporn Benyapa Kaewmalai Somruedee Jansongsaeng Vishnu Nayak Badavath Thanaphon Saelee Thamonwan Chokmahasarn Tanatorn Khotavivattana Yasuteru Shigeta Thanyada Rungrotmongkol Siwaporn Boonyasuppayakorn Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
description	A flavonoid is a versatile core structure with various cellular, immunological, and pharmacological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically modified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC<sub>50</sub> of 2.36 ± 0.22, and 10.55 ± 3.37 µM, respectively, while the cytotoxicities were similar to the original apigenin at the CC<sub>50</sub> of 70.34 ± 11.79, and 82.82 ± 11.68 µM, respectively. Molecular docking confirmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.
format	article
author	Kowit Hengphasatporn Benyapa Kaewmalai Somruedee Jansongsaeng Vishnu Nayak Badavath Thanaphon Saelee Thamonwan Chokmahasarn Tanatorn Khotavivattana Yasuteru Shigeta Thanyada Rungrotmongkol Siwaporn Boonyasuppayakorn
author_facet	Kowit Hengphasatporn Benyapa Kaewmalai Somruedee Jansongsaeng Vishnu Nayak Badavath Thanaphon Saelee Thamonwan Chokmahasarn Tanatorn Khotavivattana Yasuteru Shigeta Thanyada Rungrotmongkol Siwaporn Boonyasuppayakorn
author_sort	Kowit Hengphasatporn
title	Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
title_short	Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
title_full	Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
title_fullStr	Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
title_full_unstemmed	Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads
title_sort	alkyne-tagged apigenin, a chemical tool to navigate potential targets of flavonoid anti-dengue leads
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9ef2328a0bef47d48ff89b7f6333eafa
work_keys_str_mv	AT kowithengphasatporn alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT benyapakaewmalai alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT somruedeejansongsaeng alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT vishnunayakbadavath alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT thanaphonsaelee alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT thamonwanchokmahasarn alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT tanatornkhotavivattana alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT yasuterushigeta alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT thanyadarungrotmongkol alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads AT siwapornboonyasuppayakorn alkynetaggedapigeninachemicaltooltonavigatepotentialtargetsofflavonoidantidengueleads
_version_	1718411095001006080

Alkyne-Tagged Apigenin, a Chemical Tool to Navigate Potential Targets of Flavonoid Anti-Dengue Leads

Ejemplares similares