Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study
In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC 5...
Gespeichert in:
| Veröffentlicht in: | MedChemComm 2023-03, Vol.14 (3), p.52-533 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 533 |
|---|---|
| container_issue | 3 |
| container_start_page | 52 |
| container_title | MedChemComm |
| container_volume | 14 |
| creator | Moghadam Farid, Sara Iraji, Aida Mojtabavi, Somayeh Ghasemi, Mehrnaz Faramarzi, Mohammad Ali Mahdavi, Mohammad Barazandeh Tehrani, Maliheh Akbarzadeh, Tahmineh Saeedi, Mina |
| description | In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the
in vitro
screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC
50
values ranging from 4.8-140.2 μM) in comparison to acarbose (IC
50
= 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound
9c
, revealed that it inhibited α-glucosidase in a competitive mode with a
K
i
value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound
9c
, were performed to study the behavior of the
9c
-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.
In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. |
| doi_str_mv | 10.1039/d2md00297c |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1039_D2MD00297C</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2791707093</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-2d57d478a30b822d6b23a0fbdedd2007b6267c3e25f226e28873d1c5bf3841103</originalsourceid><addsrcrecordid>eNpd0ctu1DAUBuAIUdGq7YY9yBIbhCZgH09ihx2acqlUhJBgHTn2ydRDYk99WaSPwxvwIjwTmU4ZKla2fD79lv0XxVNGXzPKmzcGRkMpNEI_Kk6g5lDKWsLjB_vj4jzGDZ1RxVhdNU-KY143grIlPSl-fs3WqVs_WOcdlmwBC16mYHdHWCqNSY3WINHebfJaJYxERbL1CV0iv3-V6yFrH61REYl117azyYf4lsTJpWuMNi4IuttpPEytdwvywzpMVhPl1DDdIeUMGecrdR5UIMbrmaxJTNlMZ8VRr4aI5_frafH9w_tvq0_l1ZePl6t3V6XmXKQSTCXMUkjFaScBTN0BV7TvDBoDlIquhlpojlD1ADWClIIbpquu53LJ5r88LV7uc7fB32SMqR1t1DgMyqHPsQXRMEEFbfhMX_xHNz6H-TE7JRuoRCV3ga_2SgcfY8C-3QY7qjC1jLa78toL-HxxV95qxs_vI3M3ojnQv1XN4NkehKgP03_t8z9T9qEY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2789257580</pqid></control><display><type>article</type><title>Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study</title><source>Royal Society Of Chemistry Journals 2008-</source><source>PubMed Central</source><creator>Moghadam Farid, Sara ; Iraji, Aida ; Mojtabavi, Somayeh ; Ghasemi, Mehrnaz ; Faramarzi, Mohammad Ali ; Mahdavi, Mohammad ; Barazandeh Tehrani, Maliheh ; Akbarzadeh, Tahmineh ; Saeedi, Mina</creator><creatorcontrib>Moghadam Farid, Sara ; Iraji, Aida ; Mojtabavi, Somayeh ; Ghasemi, Mehrnaz ; Faramarzi, Mohammad Ali ; Mahdavi, Mohammad ; Barazandeh Tehrani, Maliheh ; Akbarzadeh, Tahmineh ; Saeedi, Mina</creatorcontrib><description>In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the
in vitro
screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC
50
values ranging from 4.8-140.2 μM) in comparison to acarbose (IC
50
= 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound
9c
, revealed that it inhibited α-glucosidase in a competitive mode with a
K
i
value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound
9c
, were performed to study the behavior of the
9c
-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.
In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity.</description><identifier>ISSN: 2632-8682</identifier><identifier>ISSN: 2040-2503</identifier><identifier>EISSN: 2632-8682</identifier><identifier>EISSN: 2040-2511</identifier><identifier>DOI: 10.1039/d2md00297c</identifier><identifier>PMID: 36970140</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Acarbose ; Chemical synthesis ; Diabetes mellitus ; Enzyme kinetics ; Glucosidase ; Hybrids ; Molecular docking ; Molecular dynamics ; Perturbation ; Quinazolinone ; Quinazolinones ; Triazoles ; α-Glucosidase</subject><ispartof>MedChemComm, 2023-03, Vol.14 (3), p.52-533</ispartof><rights>This journal is © The Royal Society of Chemistry.</rights><rights>Copyright Royal Society of Chemistry 2023</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-2d57d478a30b822d6b23a0fbdedd2007b6267c3e25f226e28873d1c5bf3841103</citedby><cites>FETCH-LOGICAL-c337t-2d57d478a30b822d6b23a0fbdedd2007b6267c3e25f226e28873d1c5bf3841103</cites><orcidid>0000-0002-8822-453X ; 0000-0002-4053-6331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36970140$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moghadam Farid, Sara</creatorcontrib><creatorcontrib>Iraji, Aida</creatorcontrib><creatorcontrib>Mojtabavi, Somayeh</creatorcontrib><creatorcontrib>Ghasemi, Mehrnaz</creatorcontrib><creatorcontrib>Faramarzi, Mohammad Ali</creatorcontrib><creatorcontrib>Mahdavi, Mohammad</creatorcontrib><creatorcontrib>Barazandeh Tehrani, Maliheh</creatorcontrib><creatorcontrib>Akbarzadeh, Tahmineh</creatorcontrib><creatorcontrib>Saeedi, Mina</creatorcontrib><title>Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study</title><title>MedChemComm</title><addtitle>RSC Med Chem</addtitle><description>In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the
in vitro
screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC
50
values ranging from 4.8-140.2 μM) in comparison to acarbose (IC
50
= 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound
9c
, revealed that it inhibited α-glucosidase in a competitive mode with a
K
i
value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound
9c
, were performed to study the behavior of the
9c
-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.
In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity.</description><subject>Acarbose</subject><subject>Chemical synthesis</subject><subject>Diabetes mellitus</subject><subject>Enzyme kinetics</subject><subject>Glucosidase</subject><subject>Hybrids</subject><subject>Molecular docking</subject><subject>Molecular dynamics</subject><subject>Perturbation</subject><subject>Quinazolinone</subject><subject>Quinazolinones</subject><subject>Triazoles</subject><subject>α-Glucosidase</subject><issn>2632-8682</issn><issn>2040-2503</issn><issn>2632-8682</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpd0ctu1DAUBuAIUdGq7YY9yBIbhCZgH09ihx2acqlUhJBgHTn2ydRDYk99WaSPwxvwIjwTmU4ZKla2fD79lv0XxVNGXzPKmzcGRkMpNEI_Kk6g5lDKWsLjB_vj4jzGDZ1RxVhdNU-KY143grIlPSl-fs3WqVs_WOcdlmwBC16mYHdHWCqNSY3WINHebfJaJYxERbL1CV0iv3-V6yFrH61REYl117azyYf4lsTJpWuMNi4IuttpPEytdwvywzpMVhPl1DDdIeUMGecrdR5UIMbrmaxJTNlMZ8VRr4aI5_frafH9w_tvq0_l1ZePl6t3V6XmXKQSTCXMUkjFaScBTN0BV7TvDBoDlIquhlpojlD1ADWClIIbpquu53LJ5r88LV7uc7fB32SMqR1t1DgMyqHPsQXRMEEFbfhMX_xHNz6H-TE7JRuoRCV3ga_2SgcfY8C-3QY7qjC1jLa78toL-HxxV95qxs_vI3M3ojnQv1XN4NkehKgP03_t8z9T9qEY</recordid><startdate>20230322</startdate><enddate>20230322</enddate><creator>Moghadam Farid, Sara</creator><creator>Iraji, Aida</creator><creator>Mojtabavi, Somayeh</creator><creator>Ghasemi, Mehrnaz</creator><creator>Faramarzi, Mohammad Ali</creator><creator>Mahdavi, Mohammad</creator><creator>Barazandeh Tehrani, Maliheh</creator><creator>Akbarzadeh, Tahmineh</creator><creator>Saeedi, Mina</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8822-453X</orcidid><orcidid>https://orcid.org/0000-0002-4053-6331</orcidid></search><sort><creationdate>20230322</creationdate><title>Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study</title><author>Moghadam Farid, Sara ; Iraji, Aida ; Mojtabavi, Somayeh ; Ghasemi, Mehrnaz ; Faramarzi, Mohammad Ali ; Mahdavi, Mohammad ; Barazandeh Tehrani, Maliheh ; Akbarzadeh, Tahmineh ; Saeedi, Mina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-2d57d478a30b822d6b23a0fbdedd2007b6267c3e25f226e28873d1c5bf3841103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acarbose</topic><topic>Chemical synthesis</topic><topic>Diabetes mellitus</topic><topic>Enzyme kinetics</topic><topic>Glucosidase</topic><topic>Hybrids</topic><topic>Molecular docking</topic><topic>Molecular dynamics</topic><topic>Perturbation</topic><topic>Quinazolinone</topic><topic>Quinazolinones</topic><topic>Triazoles</topic><topic>α-Glucosidase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moghadam Farid, Sara</creatorcontrib><creatorcontrib>Iraji, Aida</creatorcontrib><creatorcontrib>Mojtabavi, Somayeh</creatorcontrib><creatorcontrib>Ghasemi, Mehrnaz</creatorcontrib><creatorcontrib>Faramarzi, Mohammad Ali</creatorcontrib><creatorcontrib>Mahdavi, Mohammad</creatorcontrib><creatorcontrib>Barazandeh Tehrani, Maliheh</creatorcontrib><creatorcontrib>Akbarzadeh, Tahmineh</creatorcontrib><creatorcontrib>Saeedi, Mina</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moghadam Farid, Sara</au><au>Iraji, Aida</au><au>Mojtabavi, Somayeh</au><au>Ghasemi, Mehrnaz</au><au>Faramarzi, Mohammad Ali</au><au>Mahdavi, Mohammad</au><au>Barazandeh Tehrani, Maliheh</au><au>Akbarzadeh, Tahmineh</au><au>Saeedi, Mina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study</atitle><jtitle>MedChemComm</jtitle><addtitle>RSC Med Chem</addtitle><date>2023-03-22</date><risdate>2023</risdate><volume>14</volume><issue>3</issue><spage>52</spage><epage>533</epage><pages>52-533</pages><issn>2632-8682</issn><issn>2040-2503</issn><eissn>2632-8682</eissn><eissn>2040-2511</eissn><abstract>In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the
in vitro
screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC
50
values ranging from 4.8-140.2 μM) in comparison to acarbose (IC
50
= 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound
9c
, revealed that it inhibited α-glucosidase in a competitive mode with a
K
i
value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound
9c
, were performed to study the behavior of the
9c
-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents.
In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>36970140</pmid><doi>10.1039/d2md00297c</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0002-8822-453X</orcidid><orcidid>https://orcid.org/0000-0002-4053-6331</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2632-8682 |
| ispartof | MedChemComm, 2023-03, Vol.14 (3), p.52-533 |
| issn | 2632-8682 2040-2503 2632-8682 2040-2511 |
| language | eng |
| recordid | cdi_crossref_primary_10_1039_D2MD00297C |
| source | Royal Society Of Chemistry Journals 2008-; PubMed Central |
| subjects | Acarbose Chemical synthesis Diabetes mellitus Enzyme kinetics Glucosidase Hybrids Molecular docking Molecular dynamics Perturbation Quinazolinone Quinazolinones Triazoles α-Glucosidase |
| title | Quinazolinone-1,2,3-triazole-acetamide conjugates as potent α-glucosidase inhibitors: synthesis, enzyme inhibition, kinetic analysis, and molecular docking study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T04%3A17%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Quinazolinone-1,2,3-triazole-acetamide%20conjugates%20as%20potent%20%CE%B1-glucosidase%20inhibitors:%20synthesis,%20enzyme%20inhibition,%20kinetic%20analysis,%20and%20molecular%20docking%20study&rft.jtitle=MedChemComm&rft.au=Moghadam%20Farid,%20Sara&rft.date=2023-03-22&rft.volume=14&rft.issue=3&rft.spage=52&rft.epage=533&rft.pages=52-533&rft.issn=2632-8682&rft.eissn=2632-8682&rft_id=info:doi/10.1039/d2md00297c&rft_dat=%3Cproquest_cross%3E2791707093%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2789257580&rft_id=info:pmid/36970140&rfr_iscdi=true |