Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells
[Display omitted] Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtaine...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2022-01, Vol.53, p.116521-116521, Article 116521 |
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| creator | Piven, Yuri A. Yastrebova, Margarita A. Khamidullina, Alvina I. Scherbakov, Alexander M. Tatarskiy, Victor V. Rusanova, Julia A. Baranovsky, Alexander V. Zinovich, Veronica G. Khlebnicova, Tatyana S. Lakhvich, Fedor A. |
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Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 “client” proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies. |
| doi_str_mv | 10.1016/j.bmc.2021.116521 |
| format | Article |
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Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 “client” proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2021.116521</identifier><identifier>PMID: 34844036</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Acylation ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antiproliferative activity ; Apoptosis ; Benzisoxazoles ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Crystallography, X-Ray ; Docking ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Female ; HER2/neu (ERBB2) ; HSP90 ; HSP90 Heat-Shock Proteins - antagonists & inhibitors ; HSP90 Heat-Shock Proteins - metabolism ; Humans ; Models, Molecular ; Molecular Structure ; O-acyloximes ; Oxazoles - chemical synthesis ; Oxazoles - chemistry ; Oxazoles - pharmacology ; Oximes - chemical synthesis ; Oximes - chemistry ; Oximes - pharmacology ; Structure-Activity Relationship ; Virtual screening</subject><ispartof>Bioorganic & medicinal chemistry, 2022-01, Vol.53, p.116521-116521, Article 116521</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-137a00883183a58fef2e76a01dd01d9fb39bec00206e851baec183c460d8cbd33</citedby><cites>FETCH-LOGICAL-c353t-137a00883183a58fef2e76a01dd01d9fb39bec00206e851baec183c460d8cbd33</cites><orcidid>0000-0003-0405-9360 ; 0000-0001-8137-0625 ; 0000-0003-3640-0981 ; 0000-0002-9080-5683 ; 0000-0003-0023-6534</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2021.116521$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34844036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piven, Yuri A.</creatorcontrib><creatorcontrib>Yastrebova, Margarita A.</creatorcontrib><creatorcontrib>Khamidullina, Alvina I.</creatorcontrib><creatorcontrib>Scherbakov, Alexander M.</creatorcontrib><creatorcontrib>Tatarskiy, Victor V.</creatorcontrib><creatorcontrib>Rusanova, Julia A.</creatorcontrib><creatorcontrib>Baranovsky, Alexander V.</creatorcontrib><creatorcontrib>Zinovich, Veronica G.</creatorcontrib><creatorcontrib>Khlebnicova, Tatyana S.</creatorcontrib><creatorcontrib>Lakhvich, Fedor A.</creatorcontrib><title>Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 “client” proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies.</description><subject>Acylation</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferative activity</subject><subject>Apoptosis</subject><subject>Benzisoxazoles</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Crystallography, X-Ray</subject><subject>Docking</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Female</subject><subject>HER2/neu (ERBB2)</subject><subject>HSP90</subject><subject>HSP90 Heat-Shock Proteins - antagonists & inhibitors</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>O-acyloximes</subject><subject>Oxazoles - chemical synthesis</subject><subject>Oxazoles - chemistry</subject><subject>Oxazoles - pharmacology</subject><subject>Oximes - chemical synthesis</subject><subject>Oximes - chemistry</subject><subject>Oximes - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>Virtual screening</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFuEzEQhi0EomnKA3BBPqZSHcZrr-MVJ1QFglRRROFsee3Z4mh3XexNlfTpcZTCkcNoLt__a-Yj5C2HJQeu3m-X7eCWFVR8ybmqK_6CzLhUkgnR8JdkBo3SDHSjzsh5zlsAqGTDX5MzIbWUINSM7L7GR-zpLbPu0NsJPV2sL5lgNh16pq5WzIdfB59ii-NTyHFvn2LP5KLeXLI4Io37MGCmk033OIXxnm7uvjXANuvvFbX7kGkYaZvQ5ok6OzpM1GHf5wvyqrN9xjfPe05-flr_uN6wm9vPX64_3jAnajExLlYWQGvBtbC17rCrcKUscO_LNF0rmhZd-QoU6pq3Fl0hnVTgtWu9EHOyOPU-pPh7h3kyQ8jHC-yIcZdNpUBqIaGk5oSfUJdizgk785DCUDQYDuZo22xNsW2Ots3Jdsm8e67ftQP6f4m_egvw4QRgefIxYDLZBSwefEjoJuNj-E_9H8oLjTI</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Piven, Yuri A.</creator><creator>Yastrebova, Margarita A.</creator><creator>Khamidullina, Alvina I.</creator><creator>Scherbakov, Alexander M.</creator><creator>Tatarskiy, Victor V.</creator><creator>Rusanova, Julia A.</creator><creator>Baranovsky, Alexander V.</creator><creator>Zinovich, Veronica G.</creator><creator>Khlebnicova, Tatyana S.</creator><creator>Lakhvich, Fedor A.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0405-9360</orcidid><orcidid>https://orcid.org/0000-0001-8137-0625</orcidid><orcidid>https://orcid.org/0000-0003-3640-0981</orcidid><orcidid>https://orcid.org/0000-0002-9080-5683</orcidid><orcidid>https://orcid.org/0000-0003-0023-6534</orcidid></search><sort><creationdate>20220101</creationdate><title>Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells</title><author>Piven, Yuri A. ; Yastrebova, Margarita A. ; Khamidullina, Alvina I. ; Scherbakov, Alexander M. ; Tatarskiy, Victor V. ; Rusanova, Julia A. ; Baranovsky, Alexander V. ; Zinovich, Veronica G. ; Khlebnicova, Tatyana S. ; Lakhvich, Fedor A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-137a00883183a58fef2e76a01dd01d9fb39bec00206e851baec183c460d8cbd33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acylation</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiproliferative activity</topic><topic>Apoptosis</topic><topic>Benzisoxazoles</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Crystallography, X-Ray</topic><topic>Docking</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Female</topic><topic>HER2/neu (ERBB2)</topic><topic>HSP90</topic><topic>HSP90 Heat-Shock Proteins - antagonists & inhibitors</topic><topic>HSP90 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>O-acyloximes</topic><topic>Oxazoles - chemical synthesis</topic><topic>Oxazoles - chemistry</topic><topic>Oxazoles - pharmacology</topic><topic>Oximes - chemical synthesis</topic><topic>Oximes - chemistry</topic><topic>Oximes - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>Virtual screening</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piven, Yuri A.</creatorcontrib><creatorcontrib>Yastrebova, Margarita A.</creatorcontrib><creatorcontrib>Khamidullina, Alvina I.</creatorcontrib><creatorcontrib>Scherbakov, Alexander M.</creatorcontrib><creatorcontrib>Tatarskiy, Victor V.</creatorcontrib><creatorcontrib>Rusanova, Julia A.</creatorcontrib><creatorcontrib>Baranovsky, Alexander V.</creatorcontrib><creatorcontrib>Zinovich, Veronica G.</creatorcontrib><creatorcontrib>Khlebnicova, Tatyana S.</creatorcontrib><creatorcontrib>Lakhvich, Fedor A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piven, Yuri A.</au><au>Yastrebova, Margarita A.</au><au>Khamidullina, Alvina I.</au><au>Scherbakov, Alexander M.</au><au>Tatarskiy, Victor V.</au><au>Rusanova, Julia A.</au><au>Baranovsky, Alexander V.</au><au>Zinovich, Veronica G.</au><au>Khlebnicova, Tatyana S.</au><au>Lakhvich, Fedor A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>53</volume><spage>116521</spage><epage>116521</epage><pages>116521-116521</pages><artnum>116521</artnum><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes were designed as potential HSP90 inhibitors. A series of the compounds was synthesized by oximation of (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-ones followed by O-acylation with acylamidobenzoic acids. The obtained compounds showed an antiproliferative effect on three breast cancer cell lines (MCF7, MDA-MB-231 and HCC1954). Compound 16s exhibited high antiproliferative potency against HCC1954 breast cancer cells with the IC50 value of 6 µM was selected for in-depth evaluation. Compound 16s did not inhibit the growth of normal epithelial cells. We have demonstrated that the compound 16s can induce apoptosis in cancer cells via inhibition of HSP90 “client” proteins including a key oncogenic receptor, HER2/neu. Described here compounds can be considered for further basic and preclinical investigation as a part of HSP90/HER2-targeted therapies.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34844036</pmid><doi>10.1016/j.bmc.2021.116521</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0405-9360</orcidid><orcidid>https://orcid.org/0000-0001-8137-0625</orcidid><orcidid>https://orcid.org/0000-0003-3640-0981</orcidid><orcidid>https://orcid.org/0000-0002-9080-5683</orcidid><orcidid>https://orcid.org/0000-0003-0023-6534</orcidid></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry, 2022-01, Vol.53, p.116521-116521, Article 116521 |
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| subjects | Acylation Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antiproliferative activity Apoptosis Benzisoxazoles Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Breast Neoplasms - pathology Cell Line, Tumor Cell Proliferation - drug effects Crystallography, X-Ray Docking Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Female HER2/neu (ERBB2) HSP90 HSP90 Heat-Shock Proteins - antagonists & inhibitors HSP90 Heat-Shock Proteins - metabolism Humans Models, Molecular Molecular Structure O-acyloximes Oxazoles - chemical synthesis Oxazoles - chemistry Oxazoles - pharmacology Oximes - chemical synthesis Oximes - chemistry Oximes - pharmacology Structure-Activity Relationship Virtual screening |
| title | Novel O-acylated (E)-3-aryl-6,7-dihydrobenzisoxazol-4(5H)-one oximes targeting HSP90-HER2 axis in breast cancer cells |
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