Cargando…
Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities
[Image: see text] Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunction...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2008
|
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646871/ https://www.ncbi.nlm.nih.gov/pubmed/18646746 http://dx.doi.org/10.1021/jm8001422 |
| _version_ | 1782164900715429888 |
|---|---|
| author | Di Santo, Roberto Costi, Roberta Roux, Alessandra Miele, Gaetano Crucitti, Giuliana Cuzzucoli Iacovo, Alberto Rosi, Federica Lavecchia, Antonio Marinelli, Luciana Di Giovanni, Carmen Novellino, Ettore Palmisano, Lucia Andreotti, Mauro Amici, Roberta Galluzzo, Clementina Maria Nencioni, Lucia Palamara, Anna Teresa Pommier, Yves Marchand, Christophe |
| author_facet | Di Santo, Roberto Costi, Roberta Roux, Alessandra Miele, Gaetano Crucitti, Giuliana Cuzzucoli Iacovo, Alberto Rosi, Federica Lavecchia, Antonio Marinelli, Luciana Di Giovanni, Carmen Novellino, Ettore Palmisano, Lucia Andreotti, Mauro Amici, Roberta Galluzzo, Clementina Maria Nencioni, Lucia Palamara, Anna Teresa Pommier, Yves Marchand, Christophe |
| author_sort | Di Santo, Roberto |
| collection | PubMed |
| description | [Image: see text] Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3′-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN−DNA acceptor site without affecting the DNA donor site. |
| format | Text |
| id | pubmed-2646871 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2008 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-26468712009-03-20 Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities Di Santo, Roberto Costi, Roberta Roux, Alessandra Miele, Gaetano Crucitti, Giuliana Cuzzucoli Iacovo, Alberto Rosi, Federica Lavecchia, Antonio Marinelli, Luciana Di Giovanni, Carmen Novellino, Ettore Palmisano, Lucia Andreotti, Mauro Amici, Roberta Galluzzo, Clementina Maria Nencioni, Lucia Palamara, Anna Teresa Pommier, Yves Marchand, Christophe J Med Chem [Image: see text] Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3′-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN−DNA acceptor site without affecting the DNA donor site. American Chemical Society 2008-07-23 2008-08-14 /pmc/articles/PMC2646871/ /pubmed/18646746 http://dx.doi.org/10.1021/jm8001422 Text en Copyright © 2008 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75 |
| spellingShingle | Di Santo, Roberto Costi, Roberta Roux, Alessandra Miele, Gaetano Crucitti, Giuliana Cuzzucoli Iacovo, Alberto Rosi, Federica Lavecchia, Antonio Marinelli, Luciana Di Giovanni, Carmen Novellino, Ettore Palmisano, Lucia Andreotti, Mauro Amici, Roberta Galluzzo, Clementina Maria Nencioni, Lucia Palamara, Anna Teresa Pommier, Yves Marchand, Christophe Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title | Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title_full | Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title_fullStr | Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title_full_unstemmed | Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title_short | Novel Quinolinonyl Diketo Acid Derivatives as HIV-1 Integrase Inhibitors: Design, Synthesis, and Biological Activities |
| title_sort | novel quinolinonyl diketo acid derivatives as hiv-1 integrase inhibitors: design, synthesis, and biological activities |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646871/ https://www.ncbi.nlm.nih.gov/pubmed/18646746 http://dx.doi.org/10.1021/jm8001422 |
| work_keys_str_mv | AT disantoroberto novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT costiroberta novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT rouxalessandra novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT mielegaetano novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT crucittigiulianacuzzucoli novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT iacovoalberto novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT rosifederica novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT lavecchiaantonio novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT marinelliluciana novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT digiovannicarmen novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT novellinoettore novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT palmisanolucia novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT andreottimauro novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT amiciroberta novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT galluzzoclementinamaria novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT nencionilucia novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT palamaraannateresa novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT pommieryves novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities AT marchandchristophe novelquinolinonyldiketoacidderivativesashiv1integraseinhibitorsdesignsynthesisandbiologicalactivities |