Molecular hybridization based design and synthesis of new benzo[5,6]chromeno[2,3-b]-quinolin-13(14H)-one analogs as cholinesterase inhibitors
A Series of new tacrine analogs were designed, synthesized, characterized by respective spectral data and evaluated for cholinesterase inhibitory activity to be useful in Alzheimer’s disease. Most of the synthesized compounds showed good in vitro inhibitory activities toward acetyl cholinesterase (A...
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| Veröffentlicht in: | Medicinal chemistry research 2021-03, Vol.30 (3), p.685-701 |
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| creator | Macha, Baswaraju Kulkarni, Ravindra Bagul, Chandrakant Garige, Anil Kumar Akkinepally, Raghuramrao Garlapati, Achaiah |
| description | A Series of new tacrine analogs were designed, synthesized, characterized by respective spectral data and evaluated for cholinesterase inhibitory activity to be useful in Alzheimer’s disease. Most of the synthesized compounds showed good in vitro inhibitory activities toward acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among the compounds,
6i, 6o and 6r
with increased saturated carboxylic ring size attached to the pyridine moiety and having 3,4-dihydroxy, 3,4,5-trimethoxy substituents on the aromatic ring attached at the stereogenic center have shown equal potency to that of tacrine with IC
50
values 0.65 ± 0.06, 1.32 ± 0.02 and 0.85 ± 0.05, 1.65 ± 0.12 and 0.92 ± 0.03, 1.91 ± 0.12 μM against AChE and BuChE, respectively. Standard drug tacrine exhibited IC
50
values of 0.47 ± 0.02 and 0.65 ± 0.08, while Donepezil showed IC
50
0.71 ± 0.06 and 0.31 ± 0.04 μM against AChE and BuChE, respectively. Docking studies of all the molecules disclosed close hydrogen bond interactions with the binding site. |
| doi_str_mv | 10.1007/s00044-020-02670-w |
| format | Article |
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6i, 6o and 6r
with increased saturated carboxylic ring size attached to the pyridine moiety and having 3,4-dihydroxy, 3,4,5-trimethoxy substituents on the aromatic ring attached at the stereogenic center have shown equal potency to that of tacrine with IC
50
values 0.65 ± 0.06, 1.32 ± 0.02 and 0.85 ± 0.05, 1.65 ± 0.12 and 0.92 ± 0.03, 1.91 ± 0.12 μM against AChE and BuChE, respectively. Standard drug tacrine exhibited IC
50
values of 0.47 ± 0.02 and 0.65 ± 0.08, while Donepezil showed IC
50
0.71 ± 0.06 and 0.31 ± 0.04 μM against AChE and BuChE, respectively. Docking studies of all the molecules disclosed close hydrogen bond interactions with the binding site.</description><identifier>ISSN: 1054-2523</identifier><identifier>EISSN: 1554-8120</identifier><identifier>DOI: 10.1007/s00044-020-02670-w</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Alzheimer's disease ; Analogs ; Aromatic compounds ; Binding sites ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Bioorganic Chemistry ; Chemical synthesis ; Cholinesterase ; Cholinesterase inhibitors ; Donepezil ; Hybridization ; Hydrogen bonds ; Inorganic Chemistry ; Medicinal Chemistry ; Neurodegenerative diseases ; Original Research ; Pharmacology/Toxicology ; Pyridines ; Tacrine</subject><ispartof>Medicinal chemistry research, 2021-03, Vol.30 (3), p.685-701</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c319t-69f84fb0745485d4bea265192ed08faea9389fe95f5911c697a9e4c5696923a53</citedby><cites>FETCH-LOGICAL-c319t-69f84fb0745485d4bea265192ed08faea9389fe95f5911c697a9e4c5696923a53</cites><orcidid>0000-0002-6699-4744</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00044-020-02670-w$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00044-020-02670-w$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Macha, Baswaraju</creatorcontrib><creatorcontrib>Kulkarni, Ravindra</creatorcontrib><creatorcontrib>Bagul, Chandrakant</creatorcontrib><creatorcontrib>Garige, Anil Kumar</creatorcontrib><creatorcontrib>Akkinepally, Raghuramrao</creatorcontrib><creatorcontrib>Garlapati, Achaiah</creatorcontrib><title>Molecular hybridization based design and synthesis of new benzo[5,6]chromeno[2,3-b]-quinolin-13(14H)-one analogs as cholinesterase inhibitors</title><title>Medicinal chemistry research</title><addtitle>Med Chem Res</addtitle><description>A Series of new tacrine analogs were designed, synthesized, characterized by respective spectral data and evaluated for cholinesterase inhibitory activity to be useful in Alzheimer’s disease. Most of the synthesized compounds showed good in vitro inhibitory activities toward acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among the compounds,
6i, 6o and 6r
with increased saturated carboxylic ring size attached to the pyridine moiety and having 3,4-dihydroxy, 3,4,5-trimethoxy substituents on the aromatic ring attached at the stereogenic center have shown equal potency to that of tacrine with IC
50
values 0.65 ± 0.06, 1.32 ± 0.02 and 0.85 ± 0.05, 1.65 ± 0.12 and 0.92 ± 0.03, 1.91 ± 0.12 μM against AChE and BuChE, respectively. Standard drug tacrine exhibited IC
50
values of 0.47 ± 0.02 and 0.65 ± 0.08, while Donepezil showed IC
50
0.71 ± 0.06 and 0.31 ± 0.04 μM against AChE and BuChE, respectively. Docking studies of all the molecules disclosed close hydrogen bond interactions with the binding site.</description><subject>Alzheimer's disease</subject><subject>Analogs</subject><subject>Aromatic compounds</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bioorganic Chemistry</subject><subject>Chemical synthesis</subject><subject>Cholinesterase</subject><subject>Cholinesterase inhibitors</subject><subject>Donepezil</subject><subject>Hybridization</subject><subject>Hydrogen bonds</subject><subject>Inorganic Chemistry</subject><subject>Medicinal Chemistry</subject><subject>Neurodegenerative diseases</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Pyridines</subject><subject>Tacrine</subject><issn>1054-2523</issn><issn>1554-8120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp9UMtKxTAQLaLg8wdcBdwoGJ282mYp4gsUN7oSCWk7vY3URJNeLtd_8J-NXsGdi2FmmHPOHE5R7DM4YQDVaQIAKSlwyFVWQBdrxRZTStKacVjPM-SZKy42i-2UXgBEBVJtFZ93YcR2PtpIhmUTXec-7OSCJ41N2JEOk5t5Yn1H0tJPQ14TCT3xuCAN-o_wpI7L53aI4RV9eOLHgjbP9H3ufBidp0wcMnl9RIPHrGHHMEvEJtIO31dME8b8hTg_uMZNIabdYqO3Y8K9375TPF5ePJxf09v7q5vzs1vaCqYnWuq-ln0DlVSyVp1s0PJSMc2xg7q3aLWodY9a9Uoz1pa6shplq0pdai6sEjvFwUr3LYb3eTZiXsI8ZoPJcFlryFKizCi-QrUxpBSxN2_Rvdq4NAzMd-xmFbvJsZuf2M0ik8SKlDLYzzD-Sf_D-gLP_oa9</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Macha, Baswaraju</creator><creator>Kulkarni, Ravindra</creator><creator>Bagul, Chandrakant</creator><creator>Garige, Anil Kumar</creator><creator>Akkinepally, Raghuramrao</creator><creator>Garlapati, Achaiah</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><orcidid>https://orcid.org/0000-0002-6699-4744</orcidid></search><sort><creationdate>20210301</creationdate><title>Molecular hybridization based design and synthesis of new benzo[5,6]chromeno[2,3-b]-quinolin-13(14H)-one analogs as cholinesterase inhibitors</title><author>Macha, Baswaraju ; Kulkarni, Ravindra ; Bagul, Chandrakant ; Garige, Anil Kumar ; Akkinepally, Raghuramrao ; Garlapati, Achaiah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c319t-69f84fb0745485d4bea265192ed08faea9389fe95f5911c697a9e4c5696923a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alzheimer's disease</topic><topic>Analogs</topic><topic>Aromatic compounds</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bioorganic Chemistry</topic><topic>Chemical synthesis</topic><topic>Cholinesterase</topic><topic>Cholinesterase inhibitors</topic><topic>Donepezil</topic><topic>Hybridization</topic><topic>Hydrogen bonds</topic><topic>Inorganic Chemistry</topic><topic>Medicinal Chemistry</topic><topic>Neurodegenerative diseases</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Pyridines</topic><topic>Tacrine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Macha, Baswaraju</creatorcontrib><creatorcontrib>Kulkarni, Ravindra</creatorcontrib><creatorcontrib>Bagul, Chandrakant</creatorcontrib><creatorcontrib>Garige, Anil Kumar</creatorcontrib><creatorcontrib>Akkinepally, Raghuramrao</creatorcontrib><creatorcontrib>Garlapati, Achaiah</creatorcontrib><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Medicinal chemistry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Macha, Baswaraju</au><au>Kulkarni, Ravindra</au><au>Bagul, Chandrakant</au><au>Garige, Anil Kumar</au><au>Akkinepally, Raghuramrao</au><au>Garlapati, Achaiah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular hybridization based design and synthesis of new benzo[5,6]chromeno[2,3-b]-quinolin-13(14H)-one analogs as cholinesterase inhibitors</atitle><jtitle>Medicinal chemistry research</jtitle><stitle>Med Chem Res</stitle><date>2021-03-01</date><risdate>2021</risdate><volume>30</volume><issue>3</issue><spage>685</spage><epage>701</epage><pages>685-701</pages><issn>1054-2523</issn><eissn>1554-8120</eissn><abstract>A Series of new tacrine analogs were designed, synthesized, characterized by respective spectral data and evaluated for cholinesterase inhibitory activity to be useful in Alzheimer’s disease. Most of the synthesized compounds showed good in vitro inhibitory activities toward acetyl cholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among the compounds,
6i, 6o and 6r
with increased saturated carboxylic ring size attached to the pyridine moiety and having 3,4-dihydroxy, 3,4,5-trimethoxy substituents on the aromatic ring attached at the stereogenic center have shown equal potency to that of tacrine with IC
50
values 0.65 ± 0.06, 1.32 ± 0.02 and 0.85 ± 0.05, 1.65 ± 0.12 and 0.92 ± 0.03, 1.91 ± 0.12 μM against AChE and BuChE, respectively. Standard drug tacrine exhibited IC
50
values of 0.47 ± 0.02 and 0.65 ± 0.08, while Donepezil showed IC
50
0.71 ± 0.06 and 0.31 ± 0.04 μM against AChE and BuChE, respectively. Docking studies of all the molecules disclosed close hydrogen bond interactions with the binding site.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s00044-020-02670-w</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-6699-4744</orcidid></addata></record> |
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| subjects | Alzheimer's disease Analogs Aromatic compounds Binding sites Biochemistry Biomedical and Life Sciences Biomedicine Bioorganic Chemistry Chemical synthesis Cholinesterase Cholinesterase inhibitors Donepezil Hybridization Hydrogen bonds Inorganic Chemistry Medicinal Chemistry Neurodegenerative diseases Original Research Pharmacology/Toxicology Pyridines Tacrine |
| title | Molecular hybridization based design and synthesis of new benzo[5,6]chromeno[2,3-b]-quinolin-13(14H)-one analogs as cholinesterase inhibitors |
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