The Antioxidant Additive Approach for Alzheimer’s Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators
Novel multifunctional tacrines for Alzheimer’s disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy....
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| Veröffentlicht in: | Journal of medicinal chemistry 2016-11, Vol.59 (21), p.9967-9973 |
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| container_end_page | 9973 |
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| container_issue | 21 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 59 |
| creator | Benchekroun, Mohamed Romero, Alejandro Egea, Javier León, Rafael Michalska, Patrycja Buendía, Izaskun Jimeno, María Luisa Jun, Daniel Janockova, Jana Sepsova, Vendula Soukup, Ondrej Bautista-Aguilera, Oscar M Refouvelet, Bernard Ouari, Olivier Marco-Contelles, José Ismaili, Lhassane |
| description | Novel multifunctional tacrines for Alzheimer’s disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway. |
| doi_str_mv | 10.1021/acs.jmedchem.6b01178 |
| format | Article |
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Med. Chem</addtitle><description>Novel multifunctional tacrines for Alzheimer’s disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Antioxidants - chemical synthesis</subject><subject>Antioxidants - chemistry</subject><subject>Antioxidants - pharmacology</subject><subject>Cell Death - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemical Sciences</subject><subject>Cholinesterase Inhibitors - chemical synthesis</subject><subject>Cholinesterase Inhibitors - chemistry</subject><subject>Cholinesterase Inhibitors - pharmacology</subject><subject>Cholinesterases - metabolism</subject><subject>Coumaric Acids - chemical synthesis</subject><subject>Coumaric Acids - chemistry</subject><subject>Coumaric Acids - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Melatonin - chemical synthesis</subject><subject>Melatonin - chemistry</subject><subject>Melatonin - pharmacology</subject><subject>Molecular Structure</subject><subject>NF-E2-Related Factor 2 - agonists</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uc1u1DAYtBCILoU3QOg7diWy-CfrpNyibZdWSguH5Rx9sR3FJRtHdlJYTrxGX68PwDPgZduKEyfb45n55tMQ8pbRBaOcfUAVFjdbo1VrtgtZU8ay_BmZsSWnSZrT9DmZUcp5wiUXR-RVCDeUUsG4eEmOeJYJSSWbkd-b1kDRj9b9sBr7EQqt7WhvIzgM3qFqoXEeiu5na-zW-PtfdwHObDAYDEStx2H3Ea7Nd1gbP3VWwUlpB2fVHAplNXzppgBXpsPR9baHK6dtY42GDSpvexMAA6xa1-3vY3QLEbrsW1vb0fnwPo7yRo3_Jowg9hquJ9UZ9LBGFZlwcu53Y-ud1cmZ8TG_Bj5PSvvNAI9J4ka4N3xNXjTYBfPm4TwmX9fnm9VFUn7-dLkqygRFzsfESMma-jSjqaJ1LmS2zFVdo5aMoRBNgzXyRuul5vFVS81Pea5zwRE5o_kSxTGZH3xb7KrB2y36XeXQVhdFWe0xytJYgMxvWeSmB67yLgRvmicBo9W-6ipWXT1WXT1UHWXvDrJhquPfk-ix20igB8JfuZt8Hzf-v-cfI8G9Iw</recordid><startdate>20161110</startdate><enddate>20161110</enddate><creator>Benchekroun, Mohamed</creator><creator>Romero, Alejandro</creator><creator>Egea, Javier</creator><creator>León, Rafael</creator><creator>Michalska, Patrycja</creator><creator>Buendía, Izaskun</creator><creator>Jimeno, María Luisa</creator><creator>Jun, Daniel</creator><creator>Janockova, Jana</creator><creator>Sepsova, Vendula</creator><creator>Soukup, Ondrej</creator><creator>Bautista-Aguilera, Oscar M</creator><creator>Refouvelet, Bernard</creator><creator>Ouari, Olivier</creator><creator>Marco-Contelles, José</creator><creator>Ismaili, Lhassane</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-6376-8701</orcidid><orcidid>https://orcid.org/0000-0002-6013-3150</orcidid><orcidid>https://orcid.org/0000-0002-0882-6304</orcidid><orcidid>https://orcid.org/0000-0002-2034-1860</orcidid></search><sort><creationdate>20161110</creationdate><title>The Antioxidant Additive Approach for Alzheimer’s Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators</title><author>Benchekroun, Mohamed ; Romero, Alejandro ; Egea, Javier ; León, Rafael ; Michalska, Patrycja ; Buendía, Izaskun ; Jimeno, María Luisa ; Jun, Daniel ; Janockova, Jana ; Sepsova, Vendula ; Soukup, Ondrej ; Bautista-Aguilera, Oscar M ; Refouvelet, Bernard ; Ouari, Olivier ; Marco-Contelles, José ; Ismaili, Lhassane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a382t-e661fb9704c0b836758cbbad611a33ffaba2fdd5d233fb6d2928d832aa21085a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Antioxidants - chemical synthesis</topic><topic>Antioxidants - chemistry</topic><topic>Antioxidants - pharmacology</topic><topic>Cell Death - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chemical Sciences</topic><topic>Cholinesterase Inhibitors - chemical synthesis</topic><topic>Cholinesterase Inhibitors - chemistry</topic><topic>Cholinesterase Inhibitors - pharmacology</topic><topic>Cholinesterases - metabolism</topic><topic>Coumaric Acids - chemical synthesis</topic><topic>Coumaric Acids - chemistry</topic><topic>Coumaric Acids - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Melatonin - chemical synthesis</topic><topic>Melatonin - chemistry</topic><topic>Melatonin - pharmacology</topic><topic>Molecular Structure</topic><topic>NF-E2-Related Factor 2 - agonists</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Benchekroun, Mohamed</creatorcontrib><creatorcontrib>Romero, Alejandro</creatorcontrib><creatorcontrib>Egea, Javier</creatorcontrib><creatorcontrib>León, Rafael</creatorcontrib><creatorcontrib>Michalska, Patrycja</creatorcontrib><creatorcontrib>Buendía, Izaskun</creatorcontrib><creatorcontrib>Jimeno, María Luisa</creatorcontrib><creatorcontrib>Jun, Daniel</creatorcontrib><creatorcontrib>Janockova, Jana</creatorcontrib><creatorcontrib>Sepsova, Vendula</creatorcontrib><creatorcontrib>Soukup, Ondrej</creatorcontrib><creatorcontrib>Bautista-Aguilera, Oscar M</creatorcontrib><creatorcontrib>Refouvelet, Bernard</creatorcontrib><creatorcontrib>Ouari, Olivier</creatorcontrib><creatorcontrib>Marco-Contelles, José</creatorcontrib><creatorcontrib>Ismaili, Lhassane</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Benchekroun, Mohamed</au><au>Romero, Alejandro</au><au>Egea, Javier</au><au>León, Rafael</au><au>Michalska, Patrycja</au><au>Buendía, Izaskun</au><au>Jimeno, María Luisa</au><au>Jun, Daniel</au><au>Janockova, Jana</au><au>Sepsova, Vendula</au><au>Soukup, Ondrej</au><au>Bautista-Aguilera, Oscar M</au><au>Refouvelet, Bernard</au><au>Ouari, Olivier</au><au>Marco-Contelles, José</au><au>Ismaili, Lhassane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Antioxidant Additive Approach for Alzheimer’s Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2016-11-10</date><risdate>2016</risdate><volume>59</volume><issue>21</issue><spage>9967</spage><epage>9973</epage><pages>9967-9973</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>Novel multifunctional tacrines for Alzheimer’s disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>27736061</pmid><doi>10.1021/acs.jmedchem.6b01178</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-6376-8701</orcidid><orcidid>https://orcid.org/0000-0002-6013-3150</orcidid><orcidid>https://orcid.org/0000-0002-0882-6304</orcidid><orcidid>https://orcid.org/0000-0002-2034-1860</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2016-11, Vol.59 (21), p.9967-9973 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_01460668v1 |
| source | MEDLINE; ACS Publications |
| subjects | Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Antioxidants - chemical synthesis Antioxidants - chemistry Antioxidants - pharmacology Cell Death - drug effects Cell Survival - drug effects Chemical Sciences Cholinesterase Inhibitors - chemical synthesis Cholinesterase Inhibitors - chemistry Cholinesterase Inhibitors - pharmacology Cholinesterases - metabolism Coumaric Acids - chemical synthesis Coumaric Acids - chemistry Coumaric Acids - pharmacology Dose-Response Relationship, Drug Hep G2 Cells Humans Melatonin - chemical synthesis Melatonin - chemistry Melatonin - pharmacology Molecular Structure NF-E2-Related Factor 2 - agonists NF-E2-Related Factor 2 - metabolism Structure-Activity Relationship |
| title | The Antioxidant Additive Approach for Alzheimer’s Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators |
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