Synthesis of the (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids as Novel HIV-1 Reverse Transcriptase Inhibitors
The natural fatty acids (5 Z )-5-pentacosenoic and (9 Z )-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also...
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Veröffentlicht in: | Lipids 2015-09, Vol.50 (10), p.1043-1050 |
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creator | Moreira, Lizabeth Giménez Orellano, Elsie A. Rosado, Karolyna Guido, Rafael V. C. Andricopulo, Adriano D. Soto, Gabriela O. Rodríguez, José W. Sanabria-Ríos, David J. Carballeira, Néstor M. |
description | The natural fatty acids (5
Z
)-5-pentacosenoic and (9
Z
)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34-43% overall yields. The Δ
5
acids displayed the best IC
50’s
(24-38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC
50
= 12 µM). The Δ
9
acids were not as effective towards HIV-RT with the (9
Z
)-9-pentacosenoic acid displaying an IC
50
= 54 µM. Fatty acid chain length and position of the unsaturation was critical for the observed inhibition. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT. |
doi_str_mv | 10.1007/s11745-015-4064-2 |
format | Article |
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Z
)-5-pentacosenoic and (9
Z
)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34-43% overall yields. The Δ
5
acids displayed the best IC
50’s
(24-38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC
50
= 12 µM). The Δ
9
acids were not as effective towards HIV-RT with the (9
Z
)-9-pentacosenoic acid displaying an IC
50
= 54 µM. Fatty acid chain length and position of the unsaturation was critical for the observed inhibition. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT.</description><identifier>ISSN: 0024-4201</identifier><identifier>EISSN: 1558-9307</identifier><identifier>DOI: 10.1007/s11745-015-4064-2</identifier><identifier>PMID: 26345647</identifier><language>eng</language><ispartof>Lipids, 2015-09, Vol.50 (10), p.1043-1050</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids></links><search><creatorcontrib>Moreira, Lizabeth Giménez</creatorcontrib><creatorcontrib>Orellano, Elsie A.</creatorcontrib><creatorcontrib>Rosado, Karolyna</creatorcontrib><creatorcontrib>Guido, Rafael V. C.</creatorcontrib><creatorcontrib>Andricopulo, Adriano D.</creatorcontrib><creatorcontrib>Soto, Gabriela O.</creatorcontrib><creatorcontrib>Rodríguez, José W.</creatorcontrib><creatorcontrib>Sanabria-Ríos, David J.</creatorcontrib><creatorcontrib>Carballeira, Néstor M.</creatorcontrib><title>Synthesis of the (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids as Novel HIV-1 Reverse Transcriptase Inhibitors</title><title>Lipids</title><description>The natural fatty acids (5
Z
)-5-pentacosenoic and (9
Z
)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34-43% overall yields. The Δ
5
acids displayed the best IC
50’s
(24-38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC
50
= 12 µM). The Δ
9
acids were not as effective towards HIV-RT with the (9
Z
)-9-pentacosenoic acid displaying an IC
50
= 54 µM. Fatty acid chain length and position of the unsaturation was critical for the observed inhibition. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT.</description><issn>0024-4201</issn><issn>1558-9307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqljU9LxDAUxIMobv3zAbzlqIdoXvvS7l4EkZXdi4guHryEbJq1kW5S8mqh394ignj2NDO_gRnGLkBeg5TVDQFUqIQEJVCWKPIDloFSc7EoZHXIMilzFJhLmLEToo8pAi7UMZvlZYGqxCpj8WUMfePIE487Pjl-qd6uhBJPLvTGRnIhestNqPkvG7_ZnfU1cUP8MQ6u5av1qwD-7AaXyPFNMoFs8l1vprQOjd_6PiY6Y0c705I7_9FTdvuw3NyvRPe53bvaTg_JtLpLfm_SqKPx-m8TfKPf46BxjoCIxb8HvgAQPWgI</recordid><startdate>20150907</startdate><enddate>20150907</enddate><creator>Moreira, Lizabeth Giménez</creator><creator>Orellano, Elsie A.</creator><creator>Rosado, Karolyna</creator><creator>Guido, Rafael V. C.</creator><creator>Andricopulo, Adriano D.</creator><creator>Soto, Gabriela O.</creator><creator>Rodríguez, José W.</creator><creator>Sanabria-Ríos, David J.</creator><creator>Carballeira, Néstor M.</creator><scope>5PM</scope></search><sort><creationdate>20150907</creationdate><title>Synthesis of the (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids as Novel HIV-1 Reverse Transcriptase Inhibitors</title><author>Moreira, Lizabeth Giménez ; Orellano, Elsie A. ; Rosado, Karolyna ; Guido, Rafael V. C. ; Andricopulo, Adriano D. ; Soto, Gabriela O. ; Rodríguez, José W. ; Sanabria-Ríos, David J. ; Carballeira, Néstor M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_48414443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moreira, Lizabeth Giménez</creatorcontrib><creatorcontrib>Orellano, Elsie A.</creatorcontrib><creatorcontrib>Rosado, Karolyna</creatorcontrib><creatorcontrib>Guido, Rafael V. C.</creatorcontrib><creatorcontrib>Andricopulo, Adriano D.</creatorcontrib><creatorcontrib>Soto, Gabriela O.</creatorcontrib><creatorcontrib>Rodríguez, José W.</creatorcontrib><creatorcontrib>Sanabria-Ríos, David J.</creatorcontrib><creatorcontrib>Carballeira, Néstor M.</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Lipids</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moreira, Lizabeth Giménez</au><au>Orellano, Elsie A.</au><au>Rosado, Karolyna</au><au>Guido, Rafael V. C.</au><au>Andricopulo, Adriano D.</au><au>Soto, Gabriela O.</au><au>Rodríguez, José W.</au><au>Sanabria-Ríos, David J.</au><au>Carballeira, Néstor M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of the (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids as Novel HIV-1 Reverse Transcriptase Inhibitors</atitle><jtitle>Lipids</jtitle><date>2015-09-07</date><risdate>2015</risdate><volume>50</volume><issue>10</issue><spage>1043</spage><epage>1050</epage><pages>1043-1050</pages><issn>0024-4201</issn><eissn>1558-9307</eissn><abstract>The natural fatty acids (5
Z
)-5-pentacosenoic and (9
Z
)-9-pentacosenoic acids were synthesized for the first time in eight steps starting from either 4-bromo-1-butanol or 8-bromo-1-butanol and in 20-58% overall yields, while the novel fatty acids 5-pentacosynoic and 9-pentacosynoic acids were also synthesized in six steps and in 34-43% overall yields. The Δ
5
acids displayed the best IC
50’s
(24-38 µM) against the HIV-1 reverse transcriptase (RT) enzyme, comparable to nervonic acid (IC
50
= 12 µM). The Δ
9
acids were not as effective towards HIV-RT with the (9
Z
)-9-pentacosenoic acid displaying an IC
50
= 54 µM. Fatty acid chain length and position of the unsaturation was critical for the observed inhibition. Molecular modeling studies indicated the structural determinants underlying the biological activity of the most potent compounds. These results provide new insights into the structural requirements that must be present in fatty acids so as to enhance their inhibitory potential towards HIV-RT.</abstract><pmid>26345647</pmid><doi>10.1007/s11745-015-4064-2</doi></addata></record> |
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language | eng |
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source | Access via Wiley Online Library; SpringerNature Journals |
title | Synthesis of the (5Z)-5-Pentacosenoic and 5-Pentacosynoic Acids as Novel HIV-1 Reverse Transcriptase Inhibitors |
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