Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities
Asperterpenes A ( ) and B ( ), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from in very limited amounts of 3.6 mg and 1.8 mg, respectively. T...
Gespeichert in:
| Veröffentlicht in: | Chemical science (Cambridge) 2016-01, Vol.7 (10), p.6563-6572 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6572 |
|---|---|
| container_issue | 10 |
| container_start_page | 6563 |
| container_title | Chemical science (Cambridge) |
| container_volume | 7 |
| creator | Qi, Changxing Bao, Jian Wang, Jianping Zhu, Hucheng Xue, Yongbo Wang, Xiaochuan Li, Hua Sun, Weiguang Gao, Weixi Lai, Yongji Chen, Jian-Guo Zhang, Yonghui |
| description | Asperterpenes A (
) and B (
), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from
in very limited amounts of 3.6 mg and 1.8 mg, respectively. The absolute structure of
was determined using X-ray diffraction. Because of the low yield of
, a comprehensive characterization of the BACE1 inhibitory activities of
was completed
molecular biological, cell and animal studies guided by
target confirmation (ISTC). ISTC assays suggested that compounds
and
might be BACE1 inhibitors. In cell-based tests, asperterpenes A and B, as natural products, exhibited promising inhibitory activities against BACE1, with IC
values of 78 and 59 nM, respectively. LY2811376 (the positive control), one of the most potent clinical BACE1 inhibitors, has shown an IC
value of 260 nM.
, compound
exhibited activity similar to that of LY2811376 against Alzheimer's disease (AD) in 3xTg AD mice. Taken together, these findings demonstrate that asperterpene A, which contains a novel carbon skeleton, is the first terpenoid to exhibit effective BACE1 inhibitory activity. Moreover,
represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of AD. |
| doi_str_mv | 10.1039/c6sc02464e |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5131395</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1854803988</sourcerecordid><originalsourceid>FETCH-LOGICAL-c485t-8c1d90d6aa1f6072eca990dda57912db0ef1c44659949a6c8917f5ae821f78523</originalsourceid><addsrcrecordid>eNqNkcFuFDEMhiMEolXphQdAOSLULUkmySQXpO1ooUiVOADnKJt4ukEzk2mSadW3J-yWFdzqi2358y9bP0JvKbmkpNEfncyOMC45vECnjHC6kqLRL481IyfoPOdfpEbTUMHa1-iEKcLrDjlFd-s8QyqQZpgg4zW2k8dXF7g8RLxMcwIHHqYCHo-Q4oGLwWfcpzji_fJtGIYl4zpLUPNDKDt8te42FIdpF7ahxPSIrSvhPpQA-Q161dshw_lTPkM_P29-dNerm29fvnbrm5XjSpSVctRr4qW1tJekZeCsrr23otWU-S2BnjrOpdCaayud0rTthQXFaN8qwZoz9OmgOy_bEbyrXyQ7mDmF0aZHE20w_0-msDO38d4I2tBGiyrw_kkgxbsFcjFjyA6GwU4Ql2yoElxVC5R6BsqFIrRt5TNQ1ipNxF71wwF1KeacoD8eT4n5Y77p5Pdub_6mwu_-ffeI_rW6-Q3zIatJ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1827890588</pqid></control><display><type>article</type><title>Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Qi, Changxing ; Bao, Jian ; Wang, Jianping ; Zhu, Hucheng ; Xue, Yongbo ; Wang, Xiaochuan ; Li, Hua ; Sun, Weiguang ; Gao, Weixi ; Lai, Yongji ; Chen, Jian-Guo ; Zhang, Yonghui</creator><creatorcontrib>Qi, Changxing ; Bao, Jian ; Wang, Jianping ; Zhu, Hucheng ; Xue, Yongbo ; Wang, Xiaochuan ; Li, Hua ; Sun, Weiguang ; Gao, Weixi ; Lai, Yongji ; Chen, Jian-Guo ; Zhang, Yonghui</creatorcontrib><description>Asperterpenes A (
) and B (
), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from
in very limited amounts of 3.6 mg and 1.8 mg, respectively. The absolute structure of
was determined using X-ray diffraction. Because of the low yield of
, a comprehensive characterization of the BACE1 inhibitory activities of
was completed
molecular biological, cell and animal studies guided by
target confirmation (ISTC). ISTC assays suggested that compounds
and
might be BACE1 inhibitors. In cell-based tests, asperterpenes A and B, as natural products, exhibited promising inhibitory activities against BACE1, with IC
values of 78 and 59 nM, respectively. LY2811376 (the positive control), one of the most potent clinical BACE1 inhibitors, has shown an IC
value of 260 nM.
, compound
exhibited activity similar to that of LY2811376 against Alzheimer's disease (AD) in 3xTg AD mice. Taken together, these findings demonstrate that asperterpene A, which contains a novel carbon skeleton, is the first terpenoid to exhibit effective BACE1 inhibitory activity. Moreover,
represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of AD.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/c6sc02464e</identifier><identifier>PMID: 28042460</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Alzheimer's disease ; Aspergillus terreus ; Carbon ; Chemistry ; Diffraction ; In vivo tests ; Inhibitors ; Terpenes ; X-rays</subject><ispartof>Chemical science (Cambridge), 2016-01, Vol.7 (10), p.6563-6572</ispartof><rights>This journal is © The Royal Society of Chemistry 2016 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-8c1d90d6aa1f6072eca990dda57912db0ef1c44659949a6c8917f5ae821f78523</citedby><cites>FETCH-LOGICAL-c485t-8c1d90d6aa1f6072eca990dda57912db0ef1c44659949a6c8917f5ae821f78523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131395/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131395/$$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/28042460$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qi, Changxing</creatorcontrib><creatorcontrib>Bao, Jian</creatorcontrib><creatorcontrib>Wang, Jianping</creatorcontrib><creatorcontrib>Zhu, Hucheng</creatorcontrib><creatorcontrib>Xue, Yongbo</creatorcontrib><creatorcontrib>Wang, Xiaochuan</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Sun, Weiguang</creatorcontrib><creatorcontrib>Gao, Weixi</creatorcontrib><creatorcontrib>Lai, Yongji</creatorcontrib><creatorcontrib>Chen, Jian-Guo</creatorcontrib><creatorcontrib>Zhang, Yonghui</creatorcontrib><title>Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities</title><title>Chemical science (Cambridge)</title><addtitle>Chem Sci</addtitle><description>Asperterpenes A (
) and B (
), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from
in very limited amounts of 3.6 mg and 1.8 mg, respectively. The absolute structure of
was determined using X-ray diffraction. Because of the low yield of
, a comprehensive characterization of the BACE1 inhibitory activities of
was completed
molecular biological, cell and animal studies guided by
target confirmation (ISTC). ISTC assays suggested that compounds
and
might be BACE1 inhibitors. In cell-based tests, asperterpenes A and B, as natural products, exhibited promising inhibitory activities against BACE1, with IC
values of 78 and 59 nM, respectively. LY2811376 (the positive control), one of the most potent clinical BACE1 inhibitors, has shown an IC
value of 260 nM.
, compound
exhibited activity similar to that of LY2811376 against Alzheimer's disease (AD) in 3xTg AD mice. Taken together, these findings demonstrate that asperterpene A, which contains a novel carbon skeleton, is the first terpenoid to exhibit effective BACE1 inhibitory activity. Moreover,
represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of AD.</description><subject>Alzheimer's disease</subject><subject>Aspergillus terreus</subject><subject>Carbon</subject><subject>Chemistry</subject><subject>Diffraction</subject><subject>In vivo tests</subject><subject>Inhibitors</subject><subject>Terpenes</subject><subject>X-rays</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkcFuFDEMhiMEolXphQdAOSLULUkmySQXpO1ooUiVOADnKJt4ukEzk2mSadW3J-yWFdzqi2358y9bP0JvKbmkpNEfncyOMC45vECnjHC6kqLRL481IyfoPOdfpEbTUMHa1-iEKcLrDjlFd-s8QyqQZpgg4zW2k8dXF7g8RLxMcwIHHqYCHo-Q4oGLwWfcpzji_fJtGIYl4zpLUPNDKDt8te42FIdpF7ahxPSIrSvhPpQA-Q161dshw_lTPkM_P29-dNerm29fvnbrm5XjSpSVctRr4qW1tJekZeCsrr23otWU-S2BnjrOpdCaayud0rTthQXFaN8qwZoz9OmgOy_bEbyrXyQ7mDmF0aZHE20w_0-msDO38d4I2tBGiyrw_kkgxbsFcjFjyA6GwU4Ql2yoElxVC5R6BsqFIrRt5TNQ1ipNxF71wwF1KeacoD8eT4n5Y77p5Pdub_6mwu_-ffeI_rW6-Q3zIatJ</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Qi, Changxing</creator><creator>Bao, Jian</creator><creator>Wang, Jianping</creator><creator>Zhu, Hucheng</creator><creator>Xue, Yongbo</creator><creator>Wang, Xiaochuan</creator><creator>Li, Hua</creator><creator>Sun, Weiguang</creator><creator>Gao, Weixi</creator><creator>Lai, Yongji</creator><creator>Chen, Jian-Guo</creator><creator>Zhang, Yonghui</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160101</creationdate><title>Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities</title><author>Qi, Changxing ; Bao, Jian ; Wang, Jianping ; Zhu, Hucheng ; Xue, Yongbo ; Wang, Xiaochuan ; Li, Hua ; Sun, Weiguang ; Gao, Weixi ; Lai, Yongji ; Chen, Jian-Guo ; Zhang, Yonghui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-8c1d90d6aa1f6072eca990dda57912db0ef1c44659949a6c8917f5ae821f78523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alzheimer's disease</topic><topic>Aspergillus terreus</topic><topic>Carbon</topic><topic>Chemistry</topic><topic>Diffraction</topic><topic>In vivo tests</topic><topic>Inhibitors</topic><topic>Terpenes</topic><topic>X-rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qi, Changxing</creatorcontrib><creatorcontrib>Bao, Jian</creatorcontrib><creatorcontrib>Wang, Jianping</creatorcontrib><creatorcontrib>Zhu, Hucheng</creatorcontrib><creatorcontrib>Xue, Yongbo</creatorcontrib><creatorcontrib>Wang, Xiaochuan</creatorcontrib><creatorcontrib>Li, Hua</creatorcontrib><creatorcontrib>Sun, Weiguang</creatorcontrib><creatorcontrib>Gao, Weixi</creatorcontrib><creatorcontrib>Lai, Yongji</creatorcontrib><creatorcontrib>Chen, Jian-Guo</creatorcontrib><creatorcontrib>Zhang, Yonghui</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</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>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qi, Changxing</au><au>Bao, Jian</au><au>Wang, Jianping</au><au>Zhu, Hucheng</au><au>Xue, Yongbo</au><au>Wang, Xiaochuan</au><au>Li, Hua</au><au>Sun, Weiguang</au><au>Gao, Weixi</au><au>Lai, Yongji</au><au>Chen, Jian-Guo</au><au>Zhang, Yonghui</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>7</volume><issue>10</issue><spage>6563</spage><epage>6572</epage><pages>6563-6572</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>Asperterpenes A (
) and B (
), two 3,5-dimethylorsellinic acid-based meroterpenoids that contain a unique β-oriented Me-21 with an unprecedented 1,2,5-trimethyl-4,9-dioxobicyclo[3.3.1]non-2-ene-3-carboxylic acid moiety, were obtained from
in very limited amounts of 3.6 mg and 1.8 mg, respectively. The absolute structure of
was determined using X-ray diffraction. Because of the low yield of
, a comprehensive characterization of the BACE1 inhibitory activities of
was completed
molecular biological, cell and animal studies guided by
target confirmation (ISTC). ISTC assays suggested that compounds
and
might be BACE1 inhibitors. In cell-based tests, asperterpenes A and B, as natural products, exhibited promising inhibitory activities against BACE1, with IC
values of 78 and 59 nM, respectively. LY2811376 (the positive control), one of the most potent clinical BACE1 inhibitors, has shown an IC
value of 260 nM.
, compound
exhibited activity similar to that of LY2811376 against Alzheimer's disease (AD) in 3xTg AD mice. Taken together, these findings demonstrate that asperterpene A, which contains a novel carbon skeleton, is the first terpenoid to exhibit effective BACE1 inhibitory activity. Moreover,
represents a potential lead compound and a versatile scaffold for the development of drugs for the treatment of AD.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>28042460</pmid><doi>10.1039/c6sc02464e</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2041-6520 |
| ispartof | Chemical science (Cambridge), 2016-01, Vol.7 (10), p.6563-6572 |
| issn | 2041-6520 2041-6539 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5131395 |
| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Alzheimer's disease Aspergillus terreus Carbon Chemistry Diffraction In vivo tests Inhibitors Terpenes X-rays |
| title | Asperterpenes A and B, two unprecedented meroterpenoids from Aspergillus terreus with BACE1 inhibitory activities |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T04%3A57%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Asperterpenes%20A%20and%20B,%20two%20unprecedented%20meroterpenoids%20from%20Aspergillus%20terreus%20with%20BACE1%20inhibitory%20activities&rft.jtitle=Chemical%20science%20(Cambridge)&rft.au=Qi,%20Changxing&rft.date=2016-01-01&rft.volume=7&rft.issue=10&rft.spage=6563&rft.epage=6572&rft.pages=6563-6572&rft.issn=2041-6520&rft.eissn=2041-6539&rft_id=info:doi/10.1039/c6sc02464e&rft_dat=%3Cproquest_pubme%3E1854803988%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1827890588&rft_id=info:pmid/28042460&rfr_iscdi=true |