In vitro anticancer activity, toxicity and structure–activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii
The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus ( Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in n...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2011-07, Vol.254 (1), p.8-17 |
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| creator | Le Calvé, Benjamin Lallemand, Benjamin Perrone, Carmen Lenglet, Gaëlle Depauw, Sabine Van Goietsenoven, Gwendoline Bury, Marina Vurro, Maurizio Herphelin, Françoise Andolfi, Anna Zonno, Maria Chiara Mathieu, Véronique Dufrasne, François Van Antwerpen, Pierre Poumay, Yves David-Cordonnier, Marie-Hélène Evidente, Antonio Kiss, Robert |
| description | The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (
Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure–activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro. |
| doi_str_mv | 10.1016/j.taap.2011.03.027 |
| format | Article |
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Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure–activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2011.03.027</identifier><identifier>PMID: 21504755</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; Alkylation - drug effects ; ANIMALS ; Antibiotics, Antineoplastic - pharmacology ; Antibiotics, Antineoplastic - toxicity ; APOPTOSIS ; Apoptosis - drug effects ; Ascomycota - metabolism ; BODY ; BROMIDES ; BROMINE COMPOUNDS ; CALVES ; Cancer cells ; CATTLE ; Cell Cycle - drug effects ; Cell death ; Cell Line ; Cell Line, Tumor ; Cell proliferation ; Chemical stability ; DESORPTION ; DICHROISM ; DISEASES ; DNA ; DNA - metabolism ; DOMESTIC ANIMALS ; DRUGS ; FUNGI ; GLIOMAS ; GLUTATHIONE ; Glutathione - metabolism ; HALIDES ; HALOGEN COMPOUNDS ; Hemisyntheses ; Heterocyclic Compounds, 3-Ring - pharmacology ; Heterocyclic Compounds, 3-Ring - toxicity ; Humans ; IN VITRO ; IONIZATION ; LUNGS ; LYMPHATIC SYSTEM ; MAMMALS ; MASS SPECTROSCOPY ; MELTING POINTS ; Microscopy, Video ; NEOPLASMS ; Neoplasms - drug therapy ; NERVOUS SYSTEM DISEASES ; Normal cells ; NUCLEIC ACIDS ; ORGANIC COMPOUNDS ; ORGANS ; PEPTIDES ; Phyllosticta ; Phyllostictines ; PHYSICAL PROPERTIES ; PLANTS ; POLYPEPTIDES ; PROTEINS ; RADIOPROTECTIVE SUBSTANCES ; RESPIRATORY SYSTEM ; RESPONSE MODIFYING FACTORS ; RUMINANTS ; SORPTION ; SPECTROSCOPY ; Structure-Activity Relationship ; STRUCTURE-ACTIVITY RELATIONSHIPS ; THERMODYNAMIC PROPERTIES ; THYMUS ; TOXICITY ; TRANSITION TEMPERATURE ; VERTEBRATES ; Videomicroscopy</subject><ispartof>Toxicology and applied pharmacology, 2011-07, Vol.254 (1), p.8-17</ispartof><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-446a641d587137925777e9ab82bffceacb898bc7ea5a78caa6dce1c65d4a49873</citedby><cites>FETCH-LOGICAL-c415t-446a641d587137925777e9ab82bffceacb898bc7ea5a78caa6dce1c65d4a49873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2011.03.027$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21504755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/21587778$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Le Calvé, Benjamin</creatorcontrib><creatorcontrib>Lallemand, Benjamin</creatorcontrib><creatorcontrib>Perrone, Carmen</creatorcontrib><creatorcontrib>Lenglet, Gaëlle</creatorcontrib><creatorcontrib>Depauw, Sabine</creatorcontrib><creatorcontrib>Van Goietsenoven, Gwendoline</creatorcontrib><creatorcontrib>Bury, Marina</creatorcontrib><creatorcontrib>Vurro, Maurizio</creatorcontrib><creatorcontrib>Herphelin, Françoise</creatorcontrib><creatorcontrib>Andolfi, Anna</creatorcontrib><creatorcontrib>Zonno, Maria Chiara</creatorcontrib><creatorcontrib>Mathieu, Véronique</creatorcontrib><creatorcontrib>Dufrasne, François</creatorcontrib><creatorcontrib>Van Antwerpen, Pierre</creatorcontrib><creatorcontrib>Poumay, Yves</creatorcontrib><creatorcontrib>David-Cordonnier, Marie-Hélène</creatorcontrib><creatorcontrib>Evidente, Antonio</creatorcontrib><creatorcontrib>Kiss, Robert</creatorcontrib><title>In vitro anticancer activity, toxicity and structure–activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (
Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure–activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>Alkylation - drug effects</subject><subject>ANIMALS</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Antibiotics, Antineoplastic - toxicity</subject><subject>APOPTOSIS</subject><subject>Apoptosis - drug effects</subject><subject>Ascomycota - metabolism</subject><subject>BODY</subject><subject>BROMIDES</subject><subject>BROMINE COMPOUNDS</subject><subject>CALVES</subject><subject>Cancer cells</subject><subject>CATTLE</subject><subject>Cell Cycle - drug effects</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Chemical stability</subject><subject>DESORPTION</subject><subject>DICHROISM</subject><subject>DISEASES</subject><subject>DNA</subject><subject>DNA - metabolism</subject><subject>DOMESTIC ANIMALS</subject><subject>DRUGS</subject><subject>FUNGI</subject><subject>GLIOMAS</subject><subject>GLUTATHIONE</subject><subject>Glutathione - metabolism</subject><subject>HALIDES</subject><subject>HALOGEN COMPOUNDS</subject><subject>Hemisyntheses</subject><subject>Heterocyclic Compounds, 3-Ring - pharmacology</subject><subject>Heterocyclic Compounds, 3-Ring - toxicity</subject><subject>Humans</subject><subject>IN VITRO</subject><subject>IONIZATION</subject><subject>LUNGS</subject><subject>LYMPHATIC SYSTEM</subject><subject>MAMMALS</subject><subject>MASS SPECTROSCOPY</subject><subject>MELTING POINTS</subject><subject>Microscopy, Video</subject><subject>NEOPLASMS</subject><subject>Neoplasms - drug therapy</subject><subject>NERVOUS SYSTEM DISEASES</subject><subject>Normal cells</subject><subject>NUCLEIC ACIDS</subject><subject>ORGANIC COMPOUNDS</subject><subject>ORGANS</subject><subject>PEPTIDES</subject><subject>Phyllosticta</subject><subject>Phyllostictines</subject><subject>PHYSICAL PROPERTIES</subject><subject>PLANTS</subject><subject>POLYPEPTIDES</subject><subject>PROTEINS</subject><subject>RADIOPROTECTIVE SUBSTANCES</subject><subject>RESPIRATORY SYSTEM</subject><subject>RESPONSE MODIFYING FACTORS</subject><subject>RUMINANTS</subject><subject>SORPTION</subject><subject>SPECTROSCOPY</subject><subject>Structure-Activity Relationship</subject><subject>STRUCTURE-ACTIVITY RELATIONSHIPS</subject><subject>THERMODYNAMIC PROPERTIES</subject><subject>THYMUS</subject><subject>TOXICITY</subject><subject>TRANSITION TEMPERATURE</subject><subject>VERTEBRATES</subject><subject>Videomicroscopy</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEokPhBVggSyzYNMFOnMSR2FQVP5UqwQIkdtbNzQ3jIWMPtlM1rHgHnoOX4klwNC3sWNmyv3N8fU6WPRW8EFw0L3dFBDgUJRei4FXBy_ZethG8a3JeVdX9bMO5FDnn6vNJ9iiEHee8k1I8zE5KUXPZ1vUm-3Vp2bWJ3jGw0SBYJM8Ao0mHyxmL7sZg2qXbgYXoZ4yzp98_ft4hzNME0TgbtuYQmBvZYbtMkwvJLBpL7PyMAbOQZDAxdwPfIXqDC04Opq9kXUIO3g0z0sD6hcUtsXG2X-bAPvwzAobGB2MeZw9GmAI9uV1Ps09vXn-8eJdfvX97eXF-laMUdcylbKCRYqhVK6q2K-u2bamDXpX9OCIB9qpTPbYENbQKAZoBSWBTDxJkp9rqNHt-9F2f1yElQLhFZy1h1Ck8lQxVol4cqfSBbzOFqPcmIE0TWHJz0KrrRC2apklkeSTRuxA8jfrgzR78ogXXa5d6p9cu9dql5pVOXSbRs1v7ud_T8FdyV14CXh0BSlFcG_LrpJQaHIxfBx2c-Z__H2SItvE</recordid><startdate>20110701</startdate><enddate>20110701</enddate><creator>Le Calvé, Benjamin</creator><creator>Lallemand, Benjamin</creator><creator>Perrone, Carmen</creator><creator>Lenglet, Gaëlle</creator><creator>Depauw, Sabine</creator><creator>Van Goietsenoven, Gwendoline</creator><creator>Bury, Marina</creator><creator>Vurro, Maurizio</creator><creator>Herphelin, Françoise</creator><creator>Andolfi, Anna</creator><creator>Zonno, Maria Chiara</creator><creator>Mathieu, Véronique</creator><creator>Dufrasne, François</creator><creator>Van Antwerpen, Pierre</creator><creator>Poumay, Yves</creator><creator>David-Cordonnier, Marie-Hélène</creator><creator>Evidente, Antonio</creator><creator>Kiss, Robert</creator><general>Elsevier Inc</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>7ST</scope><scope>7U7</scope><scope>C1K</scope><scope>M7N</scope><scope>SOI</scope><scope>OTOTI</scope></search><sort><creationdate>20110701</creationdate><title>In vitro anticancer activity, toxicity and structure–activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii</title><author>Le Calvé, Benjamin ; Lallemand, Benjamin ; Perrone, Carmen ; Lenglet, Gaëlle ; Depauw, Sabine ; Van Goietsenoven, Gwendoline ; Bury, Marina ; Vurro, Maurizio ; Herphelin, Françoise ; Andolfi, Anna ; Zonno, Maria Chiara ; Mathieu, Véronique ; Dufrasne, François ; Van Antwerpen, Pierre ; Poumay, Yves ; David-Cordonnier, Marie-Hélène ; Evidente, Antonio ; Kiss, Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-446a641d587137925777e9ab82bffceacb898bc7ea5a78caa6dce1c65d4a49873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>Alkylation - drug effects</topic><topic>ANIMALS</topic><topic>Antibiotics, Antineoplastic - pharmacology</topic><topic>Antibiotics, Antineoplastic - toxicity</topic><topic>APOPTOSIS</topic><topic>Apoptosis - drug effects</topic><topic>Ascomycota - metabolism</topic><topic>BODY</topic><topic>BROMIDES</topic><topic>BROMINE COMPOUNDS</topic><topic>CALVES</topic><topic>Cancer cells</topic><topic>CATTLE</topic><topic>Cell Cycle - drug effects</topic><topic>Cell death</topic><topic>Cell Line</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Chemical stability</topic><topic>DESORPTION</topic><topic>DICHROISM</topic><topic>DISEASES</topic><topic>DNA</topic><topic>DNA - metabolism</topic><topic>DOMESTIC ANIMALS</topic><topic>DRUGS</topic><topic>FUNGI</topic><topic>GLIOMAS</topic><topic>GLUTATHIONE</topic><topic>Glutathione - metabolism</topic><topic>HALIDES</topic><topic>HALOGEN COMPOUNDS</topic><topic>Hemisyntheses</topic><topic>Heterocyclic Compounds, 3-Ring - pharmacology</topic><topic>Heterocyclic Compounds, 3-Ring - 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Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure–activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21504755</pmid><doi>10.1016/j.taap.2011.03.027</doi><tpages>10</tpages></addata></record> |
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| language | eng |
| recordid | cdi_osti_scitechconnect_21587778 |
| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | 60 APPLIED LIFE SCIENCES Alkylation - drug effects ANIMALS Antibiotics, Antineoplastic - pharmacology Antibiotics, Antineoplastic - toxicity APOPTOSIS Apoptosis - drug effects Ascomycota - metabolism BODY BROMIDES BROMINE COMPOUNDS CALVES Cancer cells CATTLE Cell Cycle - drug effects Cell death Cell Line Cell Line, Tumor Cell proliferation Chemical stability DESORPTION DICHROISM DISEASES DNA DNA - metabolism DOMESTIC ANIMALS DRUGS FUNGI GLIOMAS GLUTATHIONE Glutathione - metabolism HALIDES HALOGEN COMPOUNDS Hemisyntheses Heterocyclic Compounds, 3-Ring - pharmacology Heterocyclic Compounds, 3-Ring - toxicity Humans IN VITRO IONIZATION LUNGS LYMPHATIC SYSTEM MAMMALS MASS SPECTROSCOPY MELTING POINTS Microscopy, Video NEOPLASMS Neoplasms - drug therapy NERVOUS SYSTEM DISEASES Normal cells NUCLEIC ACIDS ORGANIC COMPOUNDS ORGANS PEPTIDES Phyllosticta Phyllostictines PHYSICAL PROPERTIES PLANTS POLYPEPTIDES PROTEINS RADIOPROTECTIVE SUBSTANCES RESPIRATORY SYSTEM RESPONSE MODIFYING FACTORS RUMINANTS SORPTION SPECTROSCOPY Structure-Activity Relationship STRUCTURE-ACTIVITY RELATIONSHIPS THERMODYNAMIC PROPERTIES THYMUS TOXICITY TRANSITION TEMPERATURE VERTEBRATES Videomicroscopy |
| title | In vitro anticancer activity, toxicity and structure–activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T12%3A58%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=In%20vitro%20anticancer%20activity,%20toxicity%20and%20structure%E2%80%93activity%20relationships%20of%20phyllostictine%20A,%20a%20natural%20oxazatricycloalkenone%20produced%20by%20the%20fungus%20Phyllosticta%20cirsii&rft.jtitle=Toxicology%20and%20applied%20pharmacology&rft.au=Le%20Calv%C3%A9,%20Benjamin&rft.date=2011-07-01&rft.volume=254&rft.issue=1&rft.spage=8&rft.epage=17&rft.pages=8-17&rft.issn=0041-008X&rft.eissn=1096-0333&rft_id=info:doi/10.1016/j.taap.2011.03.027&rft_dat=%3Cproquest_osti_%3E899151666%3C/proquest_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=899151666&rft_id=info:pmid/21504755&rft_els_id=S0041008X11001311&rfr_iscdi=true |