Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents
Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using...
Gespeichert in:
| Veröffentlicht in: | Medicinal chemistry research 2023, Vol.32 (2), p.342-354 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 354 |
|---|---|
| container_issue | 2 |
| container_start_page | 342 |
| container_title | Medicinal chemistry research |
| container_volume | 32 |
| creator | Wang, Hezhen Sun, Xun Wei, Chunyong Wang, Jing Xu, Yingshu Bai, Guohui Yao, Qizheng Zhang, Lei |
| description | Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative
A17
(namely tumulosic acid, also found in
Poria cocos
), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC
50
values of 7.36 ± 0.98 and 2.50 ± 0.15 μM, respectively. Further pharmacological analysis demonstrated that
A17
induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of
A17
on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition,
A17
regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that
A17
possesses great potential as an anticancer agent.
Graphical Abstract |
| doi_str_mv | 10.1007/s00044-022-03009-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9797892</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2767454360</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-29793084dcf74a9ae76a4276ac0cebc140c83c65c526d8a8c586c7cfef65d23f3</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhiMEoqXwBzggS1y4BCb-iJ0LEqqgIFXiAJwt78TZdZWNF9uJyL9ntlvKx4GLPfI8886M36p63sDrBkC_yQAgZQ2c1yAAulo8qM4bpWRtGg4PKQaKueLirHqS8w2A0CDV4-pMtKoTpjXnlf2yTmXnc8jMTT3bhOiwhCWUlfnFjbMrIU4sDuzgcLfuAzKHoWe9T2Gh3OKpLrNDLH4qwY0M1xJL_HHktvSUn1aPBjdm_-zuvqi-fXj_9fJjff356tPlu-sapZal5p3uBBjZ46Cl65zXrZOcDgT0G2wkoBHYKlS87Y0zqEyLGgc_tKrnYhAX1duT7mHe7H2P1Du50R5S2Lu02uiC_TszhZ3dxsVSY206TgKv7gRS_D77XOw-ZPTj6CYf52xpGPrNTvKO0Jf_oDdxThOtd6S0VFK0QBQ_UZhizskP98M0YI_-2ZN_lvyzt_5ZQUUv_lzjvuSXYQSIE5ApNW19-t37P7I_AeeVqJk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2767454360</pqid></control><display><type>article</type><title>Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents</title><source>SpringerLink Journals - AutoHoldings</source><creator>Wang, Hezhen ; Sun, Xun ; Wei, Chunyong ; Wang, Jing ; Xu, Yingshu ; Bai, Guohui ; Yao, Qizheng ; Zhang, Lei</creator><creatorcontrib>Wang, Hezhen ; Sun, Xun ; Wei, Chunyong ; Wang, Jing ; Xu, Yingshu ; Bai, Guohui ; Yao, Qizheng ; Zhang, Lei</creatorcontrib><description>Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative
A17
(namely tumulosic acid, also found in
Poria cocos
), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC
50
values of 7.36 ± 0.98 and 2.50 ± 0.15 μM, respectively. Further pharmacological analysis demonstrated that
A17
induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of
A17
on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition,
A17
regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that
A17
possesses great potential as an anticancer agent.
Graphical Abstract</description><identifier>ISSN: 1054-2523</identifier><identifier>EISSN: 1554-8120</identifier><identifier>DOI: 10.1007/s00044-022-03009-3</identifier><identifier>PMID: 36593868</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>AKT protein ; Anticancer properties ; Antitumor activity ; Antitumor agents ; Apoptosis ; Autophagy ; Biochemistry ; Biocompatibility ; Biological activity ; Biomedical and Life Sciences ; Biomedicine ; Bioorganic Chemistry ; Cell cycle ; Chemical synthesis ; Cholecystokinin ; Cisplatin ; Cytotoxic agents ; Cytotoxicity ; Inorganic Chemistry ; Medicinal Chemistry ; Molecular structure ; Original Research ; Pharmacology ; Pharmacology/Toxicology ; S phase ; Toxicity ; Tumor cell lines ; Western blotting</subject><ispartof>Medicinal chemistry research, 2023, Vol.32 (2), p.342-354</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-29793084dcf74a9ae76a4276ac0cebc140c83c65c526d8a8c586c7cfef65d23f3</citedby><cites>FETCH-LOGICAL-c474t-29793084dcf74a9ae76a4276ac0cebc140c83c65c526d8a8c586c7cfef65d23f3</cites><orcidid>0000-0002-6968-0492</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/s00044-022-03009-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00044-022-03009-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,778,782,883,27911,27912,41475,42544,51306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36593868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Hezhen</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><creatorcontrib>Wei, Chunyong</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Xu, Yingshu</creatorcontrib><creatorcontrib>Bai, Guohui</creatorcontrib><creatorcontrib>Yao, Qizheng</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><title>Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents</title><title>Medicinal chemistry research</title><addtitle>Med Chem Res</addtitle><addtitle>Med Chem Res</addtitle><description>Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative
A17
(namely tumulosic acid, also found in
Poria cocos
), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC
50
values of 7.36 ± 0.98 and 2.50 ± 0.15 μM, respectively. Further pharmacological analysis demonstrated that
A17
induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of
A17
on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition,
A17
regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that
A17
possesses great potential as an anticancer agent.
Graphical Abstract</description><subject>AKT protein</subject><subject>Anticancer properties</subject><subject>Antitumor activity</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Biocompatibility</subject><subject>Biological activity</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Bioorganic Chemistry</subject><subject>Cell cycle</subject><subject>Chemical synthesis</subject><subject>Cholecystokinin</subject><subject>Cisplatin</subject><subject>Cytotoxic agents</subject><subject>Cytotoxicity</subject><subject>Inorganic Chemistry</subject><subject>Medicinal Chemistry</subject><subject>Molecular structure</subject><subject>Original Research</subject><subject>Pharmacology</subject><subject>Pharmacology/Toxicology</subject><subject>S phase</subject><subject>Toxicity</subject><subject>Tumor cell lines</subject><subject>Western blotting</subject><issn>1054-2523</issn><issn>1554-8120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhiMEoqXwBzggS1y4BCb-iJ0LEqqgIFXiAJwt78TZdZWNF9uJyL9ntlvKx4GLPfI8886M36p63sDrBkC_yQAgZQ2c1yAAulo8qM4bpWRtGg4PKQaKueLirHqS8w2A0CDV4-pMtKoTpjXnlf2yTmXnc8jMTT3bhOiwhCWUlfnFjbMrIU4sDuzgcLfuAzKHoWe9T2Gh3OKpLrNDLH4qwY0M1xJL_HHktvSUn1aPBjdm_-zuvqi-fXj_9fJjff356tPlu-sapZal5p3uBBjZ46Cl65zXrZOcDgT0G2wkoBHYKlS87Y0zqEyLGgc_tKrnYhAX1duT7mHe7H2P1Du50R5S2Lu02uiC_TszhZ3dxsVSY206TgKv7gRS_D77XOw-ZPTj6CYf52xpGPrNTvKO0Jf_oDdxThOtd6S0VFK0QBQ_UZhizskP98M0YI_-2ZN_lvyzt_5ZQUUv_lzjvuSXYQSIE5ApNW19-t37P7I_AeeVqJk</recordid><startdate>2023</startdate><enddate>2023</enddate><creator>Wang, Hezhen</creator><creator>Sun, Xun</creator><creator>Wei, Chunyong</creator><creator>Wang, Jing</creator><creator>Xu, Yingshu</creator><creator>Bai, Guohui</creator><creator>Yao, Qizheng</creator><creator>Zhang, Lei</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-6968-0492</orcidid></search><sort><creationdate>2023</creationdate><title>Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents</title><author>Wang, Hezhen ; Sun, Xun ; Wei, Chunyong ; Wang, Jing ; Xu, Yingshu ; Bai, Guohui ; Yao, Qizheng ; Zhang, Lei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-29793084dcf74a9ae76a4276ac0cebc140c83c65c526d8a8c586c7cfef65d23f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>AKT protein</topic><topic>Anticancer properties</topic><topic>Antitumor activity</topic><topic>Antitumor agents</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bioorganic Chemistry</topic><topic>Cell cycle</topic><topic>Chemical synthesis</topic><topic>Cholecystokinin</topic><topic>Cisplatin</topic><topic>Cytotoxic agents</topic><topic>Cytotoxicity</topic><topic>Inorganic Chemistry</topic><topic>Medicinal Chemistry</topic><topic>Molecular structure</topic><topic>Original Research</topic><topic>Pharmacology</topic><topic>Pharmacology/Toxicology</topic><topic>S phase</topic><topic>Toxicity</topic><topic>Tumor cell lines</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Hezhen</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><creatorcontrib>Wei, Chunyong</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Xu, Yingshu</creatorcontrib><creatorcontrib>Bai, Guohui</creatorcontrib><creatorcontrib>Yao, Qizheng</creatorcontrib><creatorcontrib>Zhang, Lei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biochemistry Abstracts 1</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medicinal chemistry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Hezhen</au><au>Sun, Xun</au><au>Wei, Chunyong</au><au>Wang, Jing</au><au>Xu, Yingshu</au><au>Bai, Guohui</au><au>Yao, Qizheng</au><au>Zhang, Lei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents</atitle><jtitle>Medicinal chemistry research</jtitle><stitle>Med Chem Res</stitle><addtitle>Med Chem Res</addtitle><date>2023</date><risdate>2023</risdate><volume>32</volume><issue>2</issue><spage>342</spage><epage>354</epage><pages>342-354</pages><issn>1054-2523</issn><eissn>1554-8120</eissn><abstract>Pachymic acid, a well-known natural lanostane-type triterpenoid, exhibits various pharmacological properties. In this study, 18 derivatives of pachymic acid were synthesized by modifying their molecular structures and evaluated for their anticancer activity against two human cancer cell lines using the CCK-8 assay. Structure-activity relationship studies according to the in vitro cytotoxicity unexpectedly found one promising derivative
A17
(namely tumulosic acid, also found in
Poria cocos
), which had stronger anti-proliferative activity than the positive drug cisplatin against HepG2 and HSC-2 cell lines with IC
50
values of 7.36 ± 0.98 and 2.50 ± 0.15 μM, respectively. Further pharmacological analysis demonstrated that
A17
induced HSC-2 cell cycle arrest at the S phase, cell apoptosis, and autophagy. Western blotting confirmed the regulatory effects of
A17
on cell cycle arrest-, apoptosis-, and autophagy-related proteins expression. In addition,
A17
regulated the AKT and AMPK pathways in HSC-2 cells. These results demonstrated that
A17
possesses great potential as an anticancer agent.
Graphical Abstract</abstract><cop>New York</cop><pub>Springer US</pub><pmid>36593868</pmid><doi>10.1007/s00044-022-03009-3</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6968-0492</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1054-2523 |
| ispartof | Medicinal chemistry research, 2023, Vol.32 (2), p.342-354 |
| issn | 1054-2523 1554-8120 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9797892 |
| source | SpringerLink Journals - AutoHoldings |
| subjects | AKT protein Anticancer properties Antitumor activity Antitumor agents Apoptosis Autophagy Biochemistry Biocompatibility Biological activity Biomedical and Life Sciences Biomedicine Bioorganic Chemistry Cell cycle Chemical synthesis Cholecystokinin Cisplatin Cytotoxic agents Cytotoxicity Inorganic Chemistry Medicinal Chemistry Molecular structure Original Research Pharmacology Pharmacology/Toxicology S phase Toxicity Tumor cell lines Western blotting |
| title | Synthesis and bioactivity evaluation of pachymic acid derivatives as potential cytotoxic agents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T14%3A08%3A27IST&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=Synthesis%20and%20bioactivity%20evaluation%20of%20pachymic%20acid%20derivatives%20as%20potential%20cytotoxic%20agents&rft.jtitle=Medicinal%20chemistry%20research&rft.au=Wang,%20Hezhen&rft.date=2023&rft.volume=32&rft.issue=2&rft.spage=342&rft.epage=354&rft.pages=342-354&rft.issn=1054-2523&rft.eissn=1554-8120&rft_id=info:doi/10.1007/s00044-022-03009-3&rft_dat=%3Cproquest_pubme%3E2767454360%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=2767454360&rft_id=info:pmid/36593868&rfr_iscdi=true |