Designed Enediynes: A New Class of DNA-Cleaving Molecules with Potent and Selective Anticancer Activity
The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 1992-05, Vol.256 (5060), p.1172-1178 |
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| container_title | Science (American Association for the Advancement of Science) |
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| creator | Nicolaou, K. C. W.-M. Dai S.-C. Tsay Estevez, V. A. Wrasidlo, W. |
| description | The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents. |
| doi_str_mv | 10.1126/science.256.5060.1172 |
| format | Article |
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The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.256.5060.1172</identifier><identifier>PMID: 1589797</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>Antibiotics, Antineoplastic - chemical synthesis ; Antibiotics, Antineoplastic - pharmacology ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Antineoplastic antibiotics ; Biological and medical sciences ; Cell Line ; Cell lines ; Cell Survival - drug effects ; Chemicals ; DNA ; DNA cleavage ; DNA Damage ; Dose-Response Relationship, Drug ; Drug Design ; Enediynes ; Female ; General aspects ; Humans ; Leukemia ; Magnetic Resonance Spectroscopy ; Medical sciences ; Molecular Structure ; Pharmaceutical chemistry ; Pharmacology. Drug treatments ; Research Article ; Structure-Activity Relationship ; Tumor cell line ; Tumor Cells, Cultured ; Tumors</subject><ispartof>Science (American Association for the Advancement of Science), 1992-05, Vol.256 (5060), p.1172-1178</ispartof><rights>Copyright 1992 American Association for the Advancement of Science</rights><rights>1992 INIST-CNRS</rights><rights>COPYRIGHT 1992 American Association for the Advancement of Science</rights><rights>COPYRIGHT 1992 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science May 22, 1992</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c687t-d8bef85b7cdf1b23a6d4ca091927c0936509394aee22ecfc64e781f945d7663e3</citedby><cites>FETCH-LOGICAL-c687t-d8bef85b7cdf1b23a6d4ca091927c0936509394aee22ecfc64e781f945d7663e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/2877256$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/2877256$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,777,781,800,2871,2872,27905,27906,57998,58231</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5339819$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1589797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nicolaou, K. C.</creatorcontrib><creatorcontrib>W.-M. Dai</creatorcontrib><creatorcontrib>S.-C. Tsay</creatorcontrib><creatorcontrib>Estevez, V. A.</creatorcontrib><creatorcontrib>Wrasidlo, W.</creatorcontrib><title>Designed Enediynes: A New Class of DNA-Cleaving Molecules with Potent and Selective Anticancer Activity</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.</description><subject>Antibiotics, Antineoplastic - chemical synthesis</subject><subject>Antibiotics, Antineoplastic - pharmacology</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic antibiotics</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cell Survival - drug effects</subject><subject>Chemicals</subject><subject>DNA</subject><subject>DNA cleavage</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Enediynes</subject><subject>Female</subject><subject>General aspects</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Medical sciences</subject><subject>Molecular Structure</subject><subject>Pharmaceutical chemistry</subject><subject>Pharmacology. 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Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>1589797</pmid><doi>10.1126/science.256.5060.1172</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 1992-05, Vol.256 (5060), p.1172-1178 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_72952918 |
| source | MEDLINE; American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Antibiotics, Antineoplastic - chemical synthesis Antibiotics, Antineoplastic - pharmacology Antineoplastic agents Antineoplastic Agents - pharmacology Antineoplastic antibiotics Biological and medical sciences Cell Line Cell lines Cell Survival - drug effects Chemicals DNA DNA cleavage DNA Damage Dose-Response Relationship, Drug Drug Design Enediynes Female General aspects Humans Leukemia Magnetic Resonance Spectroscopy Medical sciences Molecular Structure Pharmaceutical chemistry Pharmacology. Drug treatments Research Article Structure-Activity Relationship Tumor cell line Tumor Cells, Cultured Tumors |
| title | Designed Enediynes: A New Class of DNA-Cleaving Molecules with Potent and Selective Anticancer Activity |
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