Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory
Based on the Gaussian-based quantitative structure-activity relationship (QSAR) and virtual screening (VS) processes, some promising acetylcholinesterase inhibitors (AChEIs) having antioxidant potential were designed synthesized, characterized, and evaluated for their ability to enhance learning and...
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| Veröffentlicht in: | European journal of medicinal chemistry 2019-02, Vol.163, p.116-135 |
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| container_title | European journal of medicinal chemistry |
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| creator | Srivastava, Pavan Tripathi, Prabhash Nath Sharma, Piyoosh Rai, Sachchida Nand Singh, Surya Pratap Srivastava, Rakesh K. Shankar, Sharmila Shrivastava, Sushant K. |
| description | Based on the Gaussian-based quantitative structure-activity relationship (QSAR) and virtual screening (VS) processes, some promising acetylcholinesterase inhibitors (AChEIs) having antioxidant potential were designed synthesized, characterized, and evaluated for their ability to enhance learning and memory. The synthesized phenyl benzoxazole derivatives exhibited significant antioxidant potential and AChE inhibitory activity, whereas the antioxidant potential of compound 34 (49.6%) was observed significantly better than standard donepezil ( |
| doi_str_mv | 10.1016/j.ejmech.2018.11.049 |
| format | Article |
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[Display omitted]
•Potential AChE inhibitors based on Gaussian-based QSAR and VS.•Synthesis and characterization of designed phenyl benzoxazole analogues.•In vitro cholinesterase inhibition assay and determination of antioxidant potential of synthesized compounds.•The most potent compound 34 was evaluated for in vivo behavioral studies in mice.•Compound 34 was evaluated for ex vivo study and biochemical analysis.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2018.11.049</identifier><identifier>PMID: 30503937</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Acetylcholinesterase ; Antioxidant ; Benzoxazole ; Butyrylcholinesterase ; QSAR</subject><ispartof>European journal of medicinal chemistry, 2019-02, Vol.163, p.116-135</ispartof><rights>2018 Elsevier Masson SAS</rights><rights>Copyright © 2018 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-45e1c44b6c2f9d4ea1da012e7d21e7e4618c4123346bf616c66e804d0908ada53</citedby><cites>FETCH-LOGICAL-c362t-45e1c44b6c2f9d4ea1da012e7d21e7e4618c4123346bf616c66e804d0908ada53</cites><orcidid>0000-0002-5500-4004</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejmech.2018.11.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30503937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Srivastava, Pavan</creatorcontrib><creatorcontrib>Tripathi, Prabhash Nath</creatorcontrib><creatorcontrib>Sharma, Piyoosh</creatorcontrib><creatorcontrib>Rai, Sachchida Nand</creatorcontrib><creatorcontrib>Singh, Surya Pratap</creatorcontrib><creatorcontrib>Srivastava, Rakesh K.</creatorcontrib><creatorcontrib>Shankar, Sharmila</creatorcontrib><creatorcontrib>Shrivastava, Sushant K.</creatorcontrib><title>Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>Based on the Gaussian-based quantitative structure-activity relationship (QSAR) and virtual screening (VS) processes, some promising acetylcholinesterase inhibitors (AChEIs) having antioxidant potential were designed synthesized, characterized, and evaluated for their ability to enhance learning and memory. The synthesized phenyl benzoxazole derivatives exhibited significant antioxidant potential and AChE inhibitory activity, whereas the antioxidant potential of compound 34 (49.6%) was observed significantly better than standard donepezil (<10%) and parallel to ascorbic acid (56.6%). Enzyme kinetics study of most potent compound 34 (AChE IC50 = 0.363 ± 0.017 μM; Ki = 0.19 ± 0.03 μM) revealed the true nature and competitive type of inhibition on AChE. The compound 34 was further assessed for in vivo and ex vivo studies and the results showed the significant reversal of cognitive deficits and antioxidant potential at the dose of 5 mg/kg comparable to standard drug donepezil.
[Display omitted]
•Potential AChE inhibitors based on Gaussian-based QSAR and VS.•Synthesis and characterization of designed phenyl benzoxazole analogues.•In vitro cholinesterase inhibition assay and determination of antioxidant potential of synthesized compounds.•The most potent compound 34 was evaluated for in vivo behavioral studies in mice.•Compound 34 was evaluated for ex vivo study and biochemical analysis.</description><subject>Acetylcholinesterase</subject><subject>Antioxidant</subject><subject>Benzoxazole</subject><subject>Butyrylcholinesterase</subject><subject>QSAR</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhi1ERZfCP0DIRy4J_oo3uSCh8tFKlbiUs-XYk8arxA62d2n6b_pP8bKFY6WR5vK-887Mg9A7SmpKqPy4q2E3gxlrRmhbU1oT0b1AG7qVbcVZI16iDWGMVw3j4hy9TmlHCGkkIa_QOScN4R3fbtDjF0juzmPtLbZwgCksM_iMw4BTmAEvI_h1wj34h3CvH8IERRbdQWd3gIR1KbyEfLRoA3mdzBgm5yFliDoBdn50vcsh4t8ujyUmu3DvbOl4iWGBmFecAwY_am8AT6Cjd_7u7z4zzCGub9DZoKcEb5_6Bfr57evt5VV18-P79eXnm8pwyXIlGqBGiF4aNnRWgKZWE8pgaxmFLQhJWyMo41zIfpBUGimhJcKSjrTa6oZfoA-nuWWvX_tygJpdMjBN2kPYJ8Wo6AgXHZNFKk5SE0NKEQa1RDfruCpK1BGO2qkTHHWEoyhVBU6xvX9K2Pcz2P-mfzSK4NNJAOXOg4OoknFQ_mJdBJOVDe75hD89dqbQ</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Srivastava, Pavan</creator><creator>Tripathi, Prabhash Nath</creator><creator>Sharma, Piyoosh</creator><creator>Rai, Sachchida Nand</creator><creator>Singh, Surya Pratap</creator><creator>Srivastava, Rakesh K.</creator><creator>Shankar, Sharmila</creator><creator>Shrivastava, Sushant K.</creator><general>Elsevier Masson SAS</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5500-4004</orcidid></search><sort><creationdate>20190201</creationdate><title>Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory</title><author>Srivastava, Pavan ; Tripathi, Prabhash Nath ; Sharma, Piyoosh ; Rai, Sachchida Nand ; Singh, Surya Pratap ; Srivastava, Rakesh K. ; Shankar, Sharmila ; Shrivastava, Sushant K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-45e1c44b6c2f9d4ea1da012e7d21e7e4618c4123346bf616c66e804d0908ada53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acetylcholinesterase</topic><topic>Antioxidant</topic><topic>Benzoxazole</topic><topic>Butyrylcholinesterase</topic><topic>QSAR</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Srivastava, Pavan</creatorcontrib><creatorcontrib>Tripathi, Prabhash Nath</creatorcontrib><creatorcontrib>Sharma, Piyoosh</creatorcontrib><creatorcontrib>Rai, Sachchida Nand</creatorcontrib><creatorcontrib>Singh, Surya Pratap</creatorcontrib><creatorcontrib>Srivastava, Rakesh K.</creatorcontrib><creatorcontrib>Shankar, Sharmila</creatorcontrib><creatorcontrib>Shrivastava, Sushant K.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Srivastava, Pavan</au><au>Tripathi, Prabhash Nath</au><au>Sharma, Piyoosh</au><au>Rai, Sachchida Nand</au><au>Singh, Surya Pratap</au><au>Srivastava, Rakesh K.</au><au>Shankar, Sharmila</au><au>Shrivastava, Sushant K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>163</volume><spage>116</spage><epage>135</epage><pages>116-135</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><abstract>Based on the Gaussian-based quantitative structure-activity relationship (QSAR) and virtual screening (VS) processes, some promising acetylcholinesterase inhibitors (AChEIs) having antioxidant potential were designed synthesized, characterized, and evaluated for their ability to enhance learning and memory. The synthesized phenyl benzoxazole derivatives exhibited significant antioxidant potential and AChE inhibitory activity, whereas the antioxidant potential of compound 34 (49.6%) was observed significantly better than standard donepezil (<10%) and parallel to ascorbic acid (56.6%). Enzyme kinetics study of most potent compound 34 (AChE IC50 = 0.363 ± 0.017 μM; Ki = 0.19 ± 0.03 μM) revealed the true nature and competitive type of inhibition on AChE. The compound 34 was further assessed for in vivo and ex vivo studies and the results showed the significant reversal of cognitive deficits and antioxidant potential at the dose of 5 mg/kg comparable to standard drug donepezil.
[Display omitted]
•Potential AChE inhibitors based on Gaussian-based QSAR and VS.•Synthesis and characterization of designed phenyl benzoxazole analogues.•In vitro cholinesterase inhibition assay and determination of antioxidant potential of synthesized compounds.•The most potent compound 34 was evaluated for in vivo behavioral studies in mice.•Compound 34 was evaluated for ex vivo study and biochemical analysis.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>30503937</pmid><doi>10.1016/j.ejmech.2018.11.049</doi><tpages>20</tpages><orcidid>https://orcid.org/0000-0002-5500-4004</orcidid></addata></record> |
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| language | eng |
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| source | Elsevier ScienceDirect Journals |
| subjects | Acetylcholinesterase Antioxidant Benzoxazole Butyrylcholinesterase QSAR |
| title | Design and development of some phenyl benzoxazole derivatives as a potent acetylcholinesterase inhibitor with antioxidant property to enhance learning and memory |
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