1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing
The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxide...
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| Veröffentlicht in: | International journal of molecular sciences 2024-11, Vol.25 (21), p.11435 |
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| creator | Shybanov, Dmitry E Kukushkin, Maxim E Grishin, Yuri K Roznyatovsky, Vitaly A Tafeenko, Viktor A Abo Qoura, Louay Pokrovsky, Vadim S Yarovaya, Olga I Belyaevskaya, Svetlana V Volobueva, Alexandrina S Esaulkova, Iana L Zarubaev, Vladimir V Beloglazkina, Elena K |
| description | The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule. A complete stereochemical assignment of 1,3-dipolar cycloaddition adducts to caryophyllene was carried out. The study of antiviral and cytotoxic activity for some heterocyclic derivatives synthesized in this work revealed relatively high biological activity of previously little-studied cycloaddition adducts at the exocyclic C=CH
bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. The activity of the compound was demonstrated up to 6 h post infection, and this could be due to slight inhibiting activity against viral neuraminidase, necessary at the stage of progeny virion budding. |
| doi_str_mv | 10.3390/ijms252111435 |
| format | Article |
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bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. The activity of the compound was demonstrated up to 6 h post infection, and this could be due to slight inhibiting activity against viral neuraminidase, necessary at the stage of progeny virion budding.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms252111435</identifier><identifier>PMID: 39518987</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antiviral Agents - chemical synthesis ; Antiviral Agents - chemistry ; Antiviral Agents - pharmacology ; Chemical properties ; Chemical research ; Chemistry ; Cycloaddition Reaction ; Cytokines ; Cytotoxicity ; Dogs ; Humans ; Imines - chemistry ; Influenza A Virus, H1N1 Subtype - drug effects ; Madin Darby Canine Kidney Cells ; Methods ; Nitriles ; Nitriles - chemistry ; Oils & fats ; Oxides - chemistry ; Pharmaceutical chemistry ; Pharmaceutical sciences ; Polycyclic Sesquiterpenes - chemical synthesis ; Polycyclic Sesquiterpenes - chemistry ; Polycyclic Sesquiterpenes - pharmacology ; Ring formation (Chemistry) ; Sesquiterpenes ; Sesquiterpenes - chemical synthesis ; Sesquiterpenes - chemistry ; Sesquiterpenes - pharmacology ; Stereochemistry ; Stereoisomerism ; Swine flu ; Tumor necrosis factor-TNF ; Viruses</subject><ispartof>International journal of molecular sciences, 2024-11, Vol.25 (21), p.11435</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c369t-6062dd34a57b24c06b0a5197e11afa78415ff69c5e3d45fa6ce55323aad0c9453</cites><orcidid>0000-0001-7709-5245 ; 0000-0002-2333-4893 ; 0000-0002-5224-3771 ; 0000-0001-5391-5077 ; 0000-0002-5673-8931</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545984/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545984/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27915,27916,53782,53784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39518987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shybanov, Dmitry E</creatorcontrib><creatorcontrib>Kukushkin, Maxim E</creatorcontrib><creatorcontrib>Grishin, Yuri K</creatorcontrib><creatorcontrib>Roznyatovsky, Vitaly A</creatorcontrib><creatorcontrib>Tafeenko, Viktor A</creatorcontrib><creatorcontrib>Abo Qoura, Louay</creatorcontrib><creatorcontrib>Pokrovsky, Vadim S</creatorcontrib><creatorcontrib>Yarovaya, Olga I</creatorcontrib><creatorcontrib>Belyaevskaya, Svetlana V</creatorcontrib><creatorcontrib>Volobueva, Alexandrina S</creatorcontrib><creatorcontrib>Esaulkova, Iana L</creatorcontrib><creatorcontrib>Zarubaev, Vladimir V</creatorcontrib><creatorcontrib>Beloglazkina, Elena K</creatorcontrib><title>1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The cycloaddition of nitrile oxides and nitrilimines to one or both of the C=C double bonds of caryophyllene is described. The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule. A complete stereochemical assignment of 1,3-dipolar cycloaddition adducts to caryophyllene was carried out. The study of antiviral and cytotoxic activity for some heterocyclic derivatives synthesized in this work revealed relatively high biological activity of previously little-studied cycloaddition adducts at the exocyclic C=CH
bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. 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The possibility of introducing five-membered fused and spiro-linked heterocycles into the structure of sesquiterpenes by the 1,3-dipolar cycloaddition reactions of nitrile oxides and nitrilimines to caryophyllene was demonstrated. As a result of these reactions, pharmacophore fragments of isoxazoline and pyrazoline are introduced into the structure of caryophyllene, which leads to an increase in the conformational rigidity of the molecule. A complete stereochemical assignment of 1,3-dipolar cycloaddition adducts to caryophyllene was carried out. The study of antiviral and cytotoxic activity for some heterocyclic derivatives synthesized in this work revealed relatively high biological activity of previously little-studied cycloaddition adducts at the exocyclic C=CH
bond of caryophyllene. The effect of substituents in the synthesized heterocycles on biological activity was demonstrated. Compounds with a good inhibitory effect on the H1N1 influenza virus were revealed. The activity of the compound was demonstrated up to 6 h post infection, and this could be due to slight inhibiting activity against viral neuraminidase, necessary at the stage of progeny virion budding.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39518987</pmid><doi>10.3390/ijms252111435</doi><orcidid>https://orcid.org/0000-0001-7709-5245</orcidid><orcidid>https://orcid.org/0000-0002-2333-4893</orcidid><orcidid>https://orcid.org/0000-0002-5224-3771</orcidid><orcidid>https://orcid.org/0000-0001-5391-5077</orcidid><orcidid>https://orcid.org/0000-0002-5673-8931</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2024-11, Vol.25 (21), p.11435 |
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| subjects | Animals Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Chemical properties Chemical research Chemistry Cycloaddition Reaction Cytokines Cytotoxicity Dogs Humans Imines - chemistry Influenza A Virus, H1N1 Subtype - drug effects Madin Darby Canine Kidney Cells Methods Nitriles Nitriles - chemistry Oils & fats Oxides - chemistry Pharmaceutical chemistry Pharmaceutical sciences Polycyclic Sesquiterpenes - chemical synthesis Polycyclic Sesquiterpenes - chemistry Polycyclic Sesquiterpenes - pharmacology Ring formation (Chemistry) Sesquiterpenes Sesquiterpenes - chemical synthesis Sesquiterpenes - chemistry Sesquiterpenes - pharmacology Stereochemistry Stereoisomerism Swine flu Tumor necrosis factor-TNF Viruses |
| title | 1,3-Dipolar Cycloaddition of Nitrile Oxides and Nitrilimines to (-)-β-Caryophyllene: Stereoselective Synthesis of Polycyclic Derivatives and Their Biological Testing |
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