Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones
Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1 H )-one (3MQ) 1 with aryl aldehydes 3a-3ad for synthesis of styrylquinoxalin-2(1 H )-ones (SQs) 4a-4ad with excellent yields. In this reaction, malononitrile activates the aldehyde via Knoevenagel condensat...
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| Veröffentlicht in: | RSC advances 2020-04, Vol.1 (27), p.15966-15975 |
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| creator | Mahajan, Sheena Slathia, Nancy Nuthakki, Vijay K Bharate, Sandip B Kapoor, Kamal K |
| description | Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1
H
)-one (3MQ)
1
with aryl aldehydes
3a-3ad
for synthesis of styrylquinoxalin-2(1
H
)-ones (SQs)
4a-4ad
with excellent yields. In this reaction, malononitrile activates the aldehyde
via
Knoevenagel condensation towards reaction with 3MQ
1
and gets liberated during the course of reaction to yield the desired SQs
4a-4ad
. The SQs were evaluated for
in vitro
cholinesterase inhibition and
4n
was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease.
SQs displaying anti-Alzheimer activity is serendipitous. Malononitrile as a handle to facilitate nucleophilic attack has been applied for the first time for the easy access of SQs. |
| doi_str_mv | 10.1039/d0ra02816a |
| format | Article |
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H
)-one (3MQ)
1
with aryl aldehydes
3a-3ad
for synthesis of styrylquinoxalin-2(1
H
)-ones (SQs)
4a-4ad
with excellent yields. In this reaction, malononitrile activates the aldehyde
via
Knoevenagel condensation towards reaction with 3MQ
1
and gets liberated during the course of reaction to yield the desired SQs
4a-4ad
. The SQs were evaluated for
in vitro
cholinesterase inhibition and
4n
was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease.
SQs displaying anti-Alzheimer activity is serendipitous. Malononitrile as a handle to facilitate nucleophilic attack has been applied for the first time for the easy access of SQs.</description><identifier>ISSN: 2046-2069</identifier><identifier>EISSN: 2046-2069</identifier><identifier>DOI: 10.1039/d0ra02816a</identifier><identifier>PMID: 35493659</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Aldehydes ; Alzheimer's disease ; Aromatic compounds ; Chemistry ; Cholinesterase ; Malononitrile ; Synthesis</subject><ispartof>RSC advances, 2020-04, Vol.1 (27), p.15966-15975</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2020</rights><rights>This journal is © The Royal Society of Chemistry 2020 The Royal Society of Chemistry</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c495t-5210209f380a0ef0105661ec0836d6741856c211c58ce6eb2abf596e5bf21caa3</citedby><cites>FETCH-LOGICAL-c495t-5210209f380a0ef0105661ec0836d6741856c211c58ce6eb2abf596e5bf21caa3</cites><orcidid>0000-0001-6081-5787 ; 0000-0002-9457-2311</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052867/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9052867/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35493659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mahajan, Sheena</creatorcontrib><creatorcontrib>Slathia, Nancy</creatorcontrib><creatorcontrib>Nuthakki, Vijay K</creatorcontrib><creatorcontrib>Bharate, Sandip B</creatorcontrib><creatorcontrib>Kapoor, Kamal K</creatorcontrib><title>Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones</title><title>RSC advances</title><addtitle>RSC Adv</addtitle><description>Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1
H
)-one (3MQ)
1
with aryl aldehydes
3a-3ad
for synthesis of styrylquinoxalin-2(1
H
)-ones (SQs)
4a-4ad
with excellent yields. In this reaction, malononitrile activates the aldehyde
via
Knoevenagel condensation towards reaction with 3MQ
1
and gets liberated during the course of reaction to yield the desired SQs
4a-4ad
. The SQs were evaluated for
in vitro
cholinesterase inhibition and
4n
was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease.
SQs displaying anti-Alzheimer activity is serendipitous. Malononitrile as a handle to facilitate nucleophilic attack has been applied for the first time for the easy access of SQs.</description><subject>Aldehydes</subject><subject>Alzheimer's disease</subject><subject>Aromatic compounds</subject><subject>Chemistry</subject><subject>Cholinesterase</subject><subject>Malononitrile</subject><subject>Synthesis</subject><issn>2046-2069</issn><issn>2046-2069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kd9rFDEQx4MottS--K6s-FKF1SS7mdu8FI76EyqC6HOcy856KXvJNckW97837dWz-uDAMAPfD19m-DL2WPBXgjf6dc8jctkJwHvsUPIWaslB37-zH7DjlC54KVBCgnjIDhrV6gaUPmTfP-EYfPAuRzdSjTa7K8zUV2n2eU3JpQp9Xzq72q7D6DylTBETVTesy3MVhirlOc7j5eR8-IkFquWJeFGHAj9iDwYcEx3fziP27d3br2cf6vPP7z-eLc9r22qVayUFl1wPTceR08AFVwCCLO8a6GHRik6BlUJY1VkCWklcDUoDqdUghUVsjtjpznc7rTbUW_I54mi20W0wziagM38r3q3Nj3BlNFeyg0UxOLk1iOFyKl-ajUuWxhE9hSkZCaqDtlX6Gn3-D3oRpujLe0Y2WokFSGgL9XJH2RhSijTsjxHcXGdn3vAvy5vslgV-evf8Pfo7qQI82QEx2b36J_yiP_ufbrb90PwCibeq1A</recordid><startdate>20200421</startdate><enddate>20200421</enddate><creator>Mahajan, Sheena</creator><creator>Slathia, Nancy</creator><creator>Nuthakki, Vijay K</creator><creator>Bharate, Sandip B</creator><creator>Kapoor, Kamal K</creator><general>Royal Society of Chemistry</general><general>The Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6081-5787</orcidid><orcidid>https://orcid.org/0000-0002-9457-2311</orcidid></search><sort><creationdate>20200421</creationdate><title>Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones</title><author>Mahajan, Sheena ; Slathia, Nancy ; Nuthakki, Vijay K ; Bharate, Sandip B ; Kapoor, Kamal K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495t-5210209f380a0ef0105661ec0836d6741856c211c58ce6eb2abf596e5bf21caa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aldehydes</topic><topic>Alzheimer's disease</topic><topic>Aromatic compounds</topic><topic>Chemistry</topic><topic>Cholinesterase</topic><topic>Malononitrile</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mahajan, Sheena</creatorcontrib><creatorcontrib>Slathia, Nancy</creatorcontrib><creatorcontrib>Nuthakki, Vijay K</creatorcontrib><creatorcontrib>Bharate, Sandip B</creatorcontrib><creatorcontrib>Kapoor, Kamal K</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>RSC advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mahajan, Sheena</au><au>Slathia, Nancy</au><au>Nuthakki, Vijay K</au><au>Bharate, Sandip B</au><au>Kapoor, Kamal K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones</atitle><jtitle>RSC advances</jtitle><addtitle>RSC Adv</addtitle><date>2020-04-21</date><risdate>2020</risdate><volume>1</volume><issue>27</issue><spage>15966</spage><epage>15975</epage><pages>15966-15975</pages><issn>2046-2069</issn><eissn>2046-2069</eissn><abstract>Herein, we report a base-free malononitrile activated condensation of 3-methylquinoxaline-2(1
H
)-one (3MQ)
1
with aryl aldehydes
3a-3ad
for synthesis of styrylquinoxalin-2(1
H
)-ones (SQs)
4a-4ad
with excellent yields. In this reaction, malononitrile activates the aldehyde
via
Knoevenagel condensation towards reaction with 3MQ
1
and gets liberated during the course of reaction to yield the desired SQs
4a-4ad
. The SQs were evaluated for
in vitro
cholinesterase inhibition and
4n
was found to display a mixed type of inhibition of AChE, which was supported by molecular modelling studies. This study has led to the discovery of a new chemotype for cholinesterase inhibition which might be useful in finding a remedy for Alzheimer's disease.
SQs displaying anti-Alzheimer activity is serendipitous. Malononitrile as a handle to facilitate nucleophilic attack has been applied for the first time for the easy access of SQs.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35493659</pmid><doi>10.1039/d0ra02816a</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-6081-5787</orcidid><orcidid>https://orcid.org/0000-0002-9457-2311</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2046-2069 |
| ispartof | RSC advances, 2020-04, Vol.1 (27), p.15966-15975 |
| issn | 2046-2069 2046-2069 |
| language | eng |
| recordid | cdi_crossref_primary_10_1039_D0RA02816A |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Aldehydes Alzheimer's disease Aromatic compounds Chemistry Cholinesterase Malononitrile Synthesis |
| title | Malononitrile-activated synthesis and anti-cholinesterase activity of styrylquinoxalin-2(1)-ones |
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