Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands
It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex c...
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Online Access: | http://hdl.handle.net/11570/3189073 https://doi.org/10.1016/j.bmc.2014.07.018 |
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ftunimessinairis:oai:iris.unime.it:11570/3189073 2024-04-21T08:01:03+00:00 Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands Sancineto L. Iraci N. Barreca M. L. Massari S. Manfroni G. Corazza G. Cecchetti V. Marcello A. Daelemans D. Pannecouque C. Tabarrini O. Sancineto, L. Iraci, N. Barreca, M. L. Massari, S. Manfroni, G. Corazza, G. Cecchetti, V. Marcello, A. Daelemans, D. Pannecouque, C. Tabarrini, O. 2014 http://hdl.handle.net/11570/3189073 https://doi.org/10.1016/j.bmc.2014.07.018 eng eng Elsevier Ltd info:eu-repo/semantics/altIdentifier/wos/WOS:000341293300015 volume:22 issue:17 firstpage:4658 lastpage:4666 numberofpages:9 journal:BIOORGANIC & MEDICINAL CHEMISTRY http://hdl.handle.net/11570/3189073 doi:10.1016/j.bmc.2014.07.018 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84906934907 6-Desfluoroquinolone Anti-HIV compound DML RT Transactivation info:eu-repo/semantics/article 2014 ftunimessinairis https://doi.org/10.1016/j.bmc.2014.07.018 2024-03-25T18:07:14Z It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. © 2014 Elsevier Ltd. All rights reserved. Article in Journal/Newspaper DML Università degli Studi di Messina: IRIS Bioorganic & Medicinal Chemistry 22 17 4658 4666 |
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Università degli Studi di Messina: IRIS |
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ftunimessinairis |
language |
English |
topic |
6-Desfluoroquinolone Anti-HIV compound DML RT Transactivation |
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6-Desfluoroquinolone Anti-HIV compound DML RT Transactivation Sancineto L. Iraci N. Barreca M. L. Massari S. Manfroni G. Corazza G. Cecchetti V. Marcello A. Daelemans D. Pannecouque C. Tabarrini O. Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
topic_facet |
6-Desfluoroquinolone Anti-HIV compound DML RT Transactivation |
description |
It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives. © 2014 Elsevier Ltd. All rights reserved. |
author2 |
Sancineto, L. Iraci, N. Barreca, M. L. Massari, S. Manfroni, G. Corazza, G. Cecchetti, V. Marcello, A. Daelemans, D. Pannecouque, C. Tabarrini, O. |
format |
Article in Journal/Newspaper |
author |
Sancineto L. Iraci N. Barreca M. L. Massari S. Manfroni G. Corazza G. Cecchetti V. Marcello A. Daelemans D. Pannecouque C. Tabarrini O. |
author_facet |
Sancineto L. Iraci N. Barreca M. L. Massari S. Manfroni G. Corazza G. Cecchetti V. Marcello A. Daelemans D. Pannecouque C. Tabarrini O. |
author_sort |
Sancineto L. |
title |
Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
title_short |
Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
title_full |
Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
title_fullStr |
Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
title_full_unstemmed |
Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands |
title_sort |
exploiting the anti-hiv 6-desfluoroquinolones to design multiple ligands |
publisher |
Elsevier Ltd |
publishDate |
2014 |
url |
http://hdl.handle.net/11570/3189073 https://doi.org/10.1016/j.bmc.2014.07.018 |
genre |
DML |
genre_facet |
DML |
op_relation |
info:eu-repo/semantics/altIdentifier/wos/WOS:000341293300015 volume:22 issue:17 firstpage:4658 lastpage:4666 numberofpages:9 journal:BIOORGANIC & MEDICINAL CHEMISTRY http://hdl.handle.net/11570/3189073 doi:10.1016/j.bmc.2014.07.018 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84906934907 |
op_doi |
https://doi.org/10.1016/j.bmc.2014.07.018 |
container_title |
Bioorganic & Medicinal Chemistry |
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22 |
container_issue |
17 |
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4658 |
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4666 |
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