Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening
SARS-CoV-2 3-chymotrypsin-like protease (3CL pro ) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The N -substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL pro inhibitor, but it has poor cell-based antiviral activity and high c...
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| Veröffentlicht in: | RSC medicinal chemistry 2023-10, Vol.14 (1), p.268-278 |
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| creator | Jiang, Xiangyi Li, Jing Viayna, Antonio Luque, F. Javier Woodson, Molly Jing, Lanlan Gao, Shenghua Zhao, Fabao Xie, Minghui Toth, Karoly Tavis, John Tollefson, Ann E Liu, Xinyong Zhan, Peng |
| description | SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The
N
-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL
pro
inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CL
pro
inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds
D1N8
(IC
50
= 0.44 ± 0.12 μM) and
D1N52
(IC
50
= 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CL
pro
, being equivalent to that of L-26 (IC
50
= 0.30 ± 0.14 μM). In addition, the cytotoxicity of
D1N8
(CC
50
>20 μM) and
D1N52
(CC
50
>20 μM) decreased significantly compared with L-26 (CC
50 |
| doi_str_mv | 10.1039/d3md00306j |
| format | Article |
| fullrecord | <record><control><sourceid>rsc</sourceid><recordid>TN_cdi_rsc_primary_d3md00306j</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>d3md00306j</sourcerecordid><originalsourceid>FETCH-rsc_primary_d3md00306j3</originalsourceid><addsrcrecordid>eNqFj8FKAzEURYMgWLQb94X3AY1mEjq0SxkUBVdW3JY0edO-OpMM74WB-gF-t7MQXLo6Fw53cZS6rcxdZdzmPro-GuNMfbpQM1s7q9f12l6pucjJGGNXVVWvNjP1_RIxFWop-EI5QW4h5RE7qJZ26XRh8l-5QyCZfIKITOO0RhTwAkMu0xu2D29b3eQPbcE1rwNnoHSkPZXMAqGj8KnDEXuSwme994IR2A8UQQIjJkqHG3XZ-k5w_strtXh6fG-eNUvYDUy95_Pur8n9538A-ZFSgg</addsrcrecordid><sourcetype>Publisher</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening</title><source>Royal Society Of Chemistry Journals 2008-</source><source>PubMed Central</source><creator>Jiang, Xiangyi ; Li, Jing ; Viayna, Antonio ; Luque, F. Javier ; Woodson, Molly ; Jing, Lanlan ; Gao, Shenghua ; Zhao, Fabao ; Xie, Minghui ; Toth, Karoly ; Tavis, John ; Tollefson, Ann E ; Liu, Xinyong ; Zhan, Peng</creator><creatorcontrib>Jiang, Xiangyi ; Li, Jing ; Viayna, Antonio ; Luque, F. Javier ; Woodson, Molly ; Jing, Lanlan ; Gao, Shenghua ; Zhao, Fabao ; Xie, Minghui ; Toth, Karoly ; Tavis, John ; Tollefson, Ann E ; Liu, Xinyong ; Zhan, Peng</creatorcontrib><description>SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The
N
-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL
pro
inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CL
pro
inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds
D1N8
(IC
50
= 0.44 ± 0.12 μM) and
D1N52
(IC
50
= 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CL
pro
, being equivalent to that of L-26 (IC
50
= 0.30 ± 0.14 μM). In addition, the cytotoxicity of
D1N8
(CC
50
>20 μM) and
D1N52
(CC
50
>20 μM) decreased significantly compared with L-26 (CC
50
<2.6 μM). Further molecular dynamics simulations revealed the potential binding interactions between
D1N52
and SARS-CoV-2 3CL
pro
. These efforts lay a solid foundation for the research of novel anti-SARS-CoV-2 agents targeting 3CL
pro
.
SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function.</description><identifier>EISSN: 2632-8682</identifier><identifier>DOI: 10.1039/d3md00306j</identifier><ispartof>RSC medicinal chemistry, 2023-10, Vol.14 (1), p.268-278</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>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Jiang, Xiangyi</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Viayna, Antonio</creatorcontrib><creatorcontrib>Luque, F. Javier</creatorcontrib><creatorcontrib>Woodson, Molly</creatorcontrib><creatorcontrib>Jing, Lanlan</creatorcontrib><creatorcontrib>Gao, Shenghua</creatorcontrib><creatorcontrib>Zhao, Fabao</creatorcontrib><creatorcontrib>Xie, Minghui</creatorcontrib><creatorcontrib>Toth, Karoly</creatorcontrib><creatorcontrib>Tavis, John</creatorcontrib><creatorcontrib>Tollefson, Ann E</creatorcontrib><creatorcontrib>Liu, Xinyong</creatorcontrib><creatorcontrib>Zhan, Peng</creatorcontrib><title>Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening</title><title>RSC medicinal chemistry</title><description>SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The
N
-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL
pro
inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CL
pro
inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds
D1N8
(IC
50
= 0.44 ± 0.12 μM) and
D1N52
(IC
50
= 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CL
pro
, being equivalent to that of L-26 (IC
50
= 0.30 ± 0.14 μM). In addition, the cytotoxicity of
D1N8
(CC
50
>20 μM) and
D1N52
(CC
50
>20 μM) decreased significantly compared with L-26 (CC
50
<2.6 μM). Further molecular dynamics simulations revealed the potential binding interactions between
D1N52
and SARS-CoV-2 3CL
pro
. These efforts lay a solid foundation for the research of novel anti-SARS-CoV-2 agents targeting 3CL
pro
.
SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function.</description><issn>2632-8682</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid/><recordid>eNqFj8FKAzEURYMgWLQb94X3AY1mEjq0SxkUBVdW3JY0edO-OpMM74WB-gF-t7MQXLo6Fw53cZS6rcxdZdzmPro-GuNMfbpQM1s7q9f12l6pucjJGGNXVVWvNjP1_RIxFWop-EI5QW4h5RE7qJZ26XRh8l-5QyCZfIKITOO0RhTwAkMu0xu2D29b3eQPbcE1rwNnoHSkPZXMAqGj8KnDEXuSwme994IR2A8UQQIjJkqHG3XZ-k5w_strtXh6fG-eNUvYDUy95_Pur8n9538A-ZFSgg</recordid><startdate>20231018</startdate><enddate>20231018</enddate><creator>Jiang, Xiangyi</creator><creator>Li, Jing</creator><creator>Viayna, Antonio</creator><creator>Luque, F. Javier</creator><creator>Woodson, Molly</creator><creator>Jing, Lanlan</creator><creator>Gao, Shenghua</creator><creator>Zhao, Fabao</creator><creator>Xie, Minghui</creator><creator>Toth, Karoly</creator><creator>Tavis, John</creator><creator>Tollefson, Ann E</creator><creator>Liu, Xinyong</creator><creator>Zhan, Peng</creator><scope/></search><sort><creationdate>20231018</creationdate><title>Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening</title><author>Jiang, Xiangyi ; Li, Jing ; Viayna, Antonio ; Luque, F. Javier ; Woodson, Molly ; Jing, Lanlan ; Gao, Shenghua ; Zhao, Fabao ; Xie, Minghui ; Toth, Karoly ; Tavis, John ; Tollefson, Ann E ; Liu, Xinyong ; Zhan, Peng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-rsc_primary_d3md00306j3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jiang, Xiangyi</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Viayna, Antonio</creatorcontrib><creatorcontrib>Luque, F. Javier</creatorcontrib><creatorcontrib>Woodson, Molly</creatorcontrib><creatorcontrib>Jing, Lanlan</creatorcontrib><creatorcontrib>Gao, Shenghua</creatorcontrib><creatorcontrib>Zhao, Fabao</creatorcontrib><creatorcontrib>Xie, Minghui</creatorcontrib><creatorcontrib>Toth, Karoly</creatorcontrib><creatorcontrib>Tavis, John</creatorcontrib><creatorcontrib>Tollefson, Ann E</creatorcontrib><creatorcontrib>Liu, Xinyong</creatorcontrib><creatorcontrib>Zhan, Peng</creatorcontrib><jtitle>RSC medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jiang, Xiangyi</au><au>Li, Jing</au><au>Viayna, Antonio</au><au>Luque, F. Javier</au><au>Woodson, Molly</au><au>Jing, Lanlan</au><au>Gao, Shenghua</au><au>Zhao, Fabao</au><au>Xie, Minghui</au><au>Toth, Karoly</au><au>Tavis, John</au><au>Tollefson, Ann E</au><au>Liu, Xinyong</au><au>Zhan, Peng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening</atitle><jtitle>RSC medicinal chemistry</jtitle><date>2023-10-18</date><risdate>2023</risdate><volume>14</volume><issue>1</issue><spage>268</spage><epage>278</epage><pages>268-278</pages><eissn>2632-8682</eissn><abstract>SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function. The
N
-substituted isatin derivative L-26 is a potential SARS-CoV-2 3CL
pro
inhibitor, but it has poor cell-based antiviral activity and high cytotoxicity. With L-26 as the lead compound, 58 isatin derivatives were prepared using click-chemistry-based miniaturized synthesis and their 3CL
pro
inhibitory activities were determined by a fluorescence resonance energy transfer-based enzymatic assay. Compounds
D1N8
(IC
50
= 0.44 ± 0.12 μM) and
D1N52
(IC
50
= 0.53 ± 0.21 μM) displayed excellent inhibitory potency against SARS-CoV-2 3CL
pro
, being equivalent to that of L-26 (IC
50
= 0.30 ± 0.14 μM). In addition, the cytotoxicity of
D1N8
(CC
50
>20 μM) and
D1N52
(CC
50
>20 μM) decreased significantly compared with L-26 (CC
50
<2.6 μM). Further molecular dynamics simulations revealed the potential binding interactions between
D1N52
and SARS-CoV-2 3CL
pro
. These efforts lay a solid foundation for the research of novel anti-SARS-CoV-2 agents targeting 3CL
pro
.
SARS-CoV-2 3-chymotrypsin-like protease (3CL
pro
) is considered an attractive target for the development of anti-COVID-19 agents due to its vital function.</abstract><doi>10.1039/d3md00306j</doi><tpages>11</tpages></addata></record> |
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| source | Royal Society Of Chemistry Journals 2008-; PubMed Central |
| title | Identification of novel 1,2,3-triazole isatin derivatives as potent SARS-CoV-2 3CLpro inhibitors click-chemistry-based rapid screening |
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