Synthesis and Biological Evaluation of 12,13-Cyclopropyl and 12,13-Cyclobutyl Epothilones
An unambiguous chemical synthesis and biological evaluation of the title compounds revealed their comparable potencies to natural epothilone A (1) against tumor cell lines, shedding further light on structure–activity relationships within the epothilone class. The picture shows a superposition of mo...
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| Veröffentlicht in: | Chembiochem : a European journal of chemical biology 2001-01, Vol.2 (1), p.69-75 |
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| creator | Nicolaou, K. C. Namoto, Kenji Li, Jim Ritzén, Andreas Ulven, Trond Shoji, Mitsuru Zaharevitz, Dan Gussio, Rick Sackett, Dan L. Ward, Rita D. Hensler, Anne Fojo, Tito Giannakakou, Paraskevi |
| description | An unambiguous chemical synthesis and biological evaluation of the title compounds revealed their comparable potencies to natural epothilone A (1) against tumor cell lines, shedding further light on structure–activity relationships within the epothilone class. The picture shows a superposition of molecular models of 1 and 12,13‐cyclopropyl epothilone A (2) (C atoms in magenta and white, respectively) in the tubulin binding site. A water molecule hydrogen‐bonded to 1 (H atoms in magenta) is displaced upon binding of 2 (H atoms in white) which makes hydrophobic interactions with the side chain of Leu 273. |
| doi_str_mv | 10.1002/1439-7633(20010105)2:1<69::AID-CBIC69>3.0.CO;2-8 |
| format | Article |
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C. ; Namoto, Kenji ; Li, Jim ; Ritzén, Andreas ; Ulven, Trond ; Shoji, Mitsuru ; Zaharevitz, Dan ; Gussio, Rick ; Sackett, Dan L. ; Ward, Rita D. ; Hensler, Anne ; Fojo, Tito ; Giannakakou, Paraskevi</creator><creatorcontrib>Nicolaou, K. C. ; Namoto, Kenji ; Li, Jim ; Ritzén, Andreas ; Ulven, Trond ; Shoji, Mitsuru ; Zaharevitz, Dan ; Gussio, Rick ; Sackett, Dan L. ; Ward, Rita D. ; Hensler, Anne ; Fojo, Tito ; Giannakakou, Paraskevi</creatorcontrib><description>An unambiguous chemical synthesis and biological evaluation of the title compounds revealed their comparable potencies to natural epothilone A (1) against tumor cell lines, shedding further light on structure–activity relationships within the epothilone class. The picture shows a superposition of molecular models of 1 and 12,13‐cyclopropyl epothilone A (2) (C atoms in magenta and white, respectively) in the tubulin binding site. 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C.</creatorcontrib><creatorcontrib>Namoto, Kenji</creatorcontrib><creatorcontrib>Li, Jim</creatorcontrib><creatorcontrib>Ritzén, Andreas</creatorcontrib><creatorcontrib>Ulven, Trond</creatorcontrib><creatorcontrib>Shoji, Mitsuru</creatorcontrib><creatorcontrib>Zaharevitz, Dan</creatorcontrib><creatorcontrib>Gussio, Rick</creatorcontrib><creatorcontrib>Sackett, Dan L.</creatorcontrib><creatorcontrib>Ward, Rita D.</creatorcontrib><creatorcontrib>Hensler, Anne</creatorcontrib><creatorcontrib>Fojo, Tito</creatorcontrib><creatorcontrib>Giannakakou, Paraskevi</creatorcontrib><title>Synthesis and Biological Evaluation of 12,13-Cyclopropyl and 12,13-Cyclobutyl Epothilones</title><title>Chembiochem : a European journal of chemical biology</title><addtitle>ChemBioChem</addtitle><description>An unambiguous chemical synthesis and biological evaluation of the title compounds revealed their comparable potencies to natural epothilone A (1) against tumor cell lines, shedding further light on structure–activity relationships within the epothilone class. 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A water molecule hydrogen‐bonded to 1 (H atoms in magenta) is displaced upon binding of 2 (H atoms in white) which makes hydrophobic interactions with the side chain of Leu 273.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>antitumor agents</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Epothilones</subject><subject>Humans</subject><subject>Indicators and Reagents</subject><subject>Lactones - chemical synthesis</subject><subject>Lactones - pharmacology</subject><subject>Microscopy, Electron</subject><subject>Models, Molecular</subject><subject>natural products</subject><subject>Stereoisomerism</subject><subject>structure-activity relationships</subject><subject>synthesis design</subject><subject>Thiazoles - chemical synthesis</subject><subject>Thiazoles - pharmacology</subject><subject>Tubulin - metabolism</subject><subject>Tubulin - ultrastructure</subject><subject>Tumor Cells, Cultured</subject><issn>1439-4227</issn><issn>1439-7633</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkMFu1DAURSMEoqXwCygrBBIZnu0ktgdUqU2HMlLpAAUh2Dw5HqcN9cRDnAD5ezwkFBZskBe2rq_Ps04UCQIzAkCfkZTJhOeMPaYAJKzsCZ2TF7mcz4-WJ0lxvCxyechmMCtWz2kibkX7N09uT-eUUr4X3fP-CwDInJG70R4hgoqUyv3o08XQdFfG1z5WzTo-rp11l7VWNl58U7ZXXe2a2FUxoU8JS4pBW7dt3Xawv-p_pWXfhXCxdd1VbV1j_P3oTqWsNw-m_SD68HLxvniVnK1Ol8XRWaKZTGViKhAgsorwUqtKMi5NCZU0TKkSBK-YYZxwqTWUawUyE1JmGqQg2VoD8JQdRI9GbvjX1974Dje118Za1RjXe-Q0pTlPRSi-GYu6dd63psJtW29UOyAB3OnGnS_cucPfujGEmEvEoBtH3cgQsFiFmx3y4TS7Lzdm_Qc4-Q2Fi7HwvbZm-I-B_5w3JYGajNTad-bHDVW115hzxjP8eH6K7z6fZG_zc4mv2U85_KWw</recordid><startdate>20010108</startdate><enddate>20010108</enddate><creator>Nicolaou, K. 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C. ; Namoto, Kenji ; Li, Jim ; Ritzén, Andreas ; Ulven, Trond ; Shoji, Mitsuru ; Zaharevitz, Dan ; Gussio, Rick ; Sackett, Dan L. ; Ward, Rita D. ; Hensler, Anne ; Fojo, Tito ; Giannakakou, Paraskevi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3949-ef08085f17bcaf9379eb0f9e3aab087f3e37179cc0bda0958995c09815dc00743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>antitumor agents</topic><topic>Drug Resistance, Neoplasm</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Epothilones</topic><topic>Humans</topic><topic>Indicators and Reagents</topic><topic>Lactones - chemical synthesis</topic><topic>Lactones - pharmacology</topic><topic>Microscopy, Electron</topic><topic>Models, Molecular</topic><topic>natural products</topic><topic>Stereoisomerism</topic><topic>structure-activity relationships</topic><topic>synthesis design</topic><topic>Thiazoles - chemical synthesis</topic><topic>Thiazoles - pharmacology</topic><topic>Tubulin - metabolism</topic><topic>Tubulin - ultrastructure</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nicolaou, K. 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The picture shows a superposition of molecular models of 1 and 12,13‐cyclopropyl epothilone A (2) (C atoms in magenta and white, respectively) in the tubulin binding site. A water molecule hydrogen‐bonded to 1 (H atoms in magenta) is displaced upon binding of 2 (H atoms in white) which makes hydrophobic interactions with the side chain of Leu 273.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag GmbH</pub><pmid>11828429</pmid><doi>10.1002/1439-7633(20010105)2:1<69::AID-CBIC69>3.0.CO;2-8</doi><tpages>7</tpages></addata></record> |
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| identifier | ISSN: 1439-4227 |
| ispartof | Chembiochem : a European journal of chemical biology, 2001-01, Vol.2 (1), p.69-75 |
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| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - pharmacology antitumor agents Drug Resistance, Neoplasm Drug Screening Assays, Antitumor Epothilones Humans Indicators and Reagents Lactones - chemical synthesis Lactones - pharmacology Microscopy, Electron Models, Molecular natural products Stereoisomerism structure-activity relationships synthesis design Thiazoles - chemical synthesis Thiazoles - pharmacology Tubulin - metabolism Tubulin - ultrastructure Tumor Cells, Cultured |
| title | Synthesis and Biological Evaluation of 12,13-Cyclopropyl and 12,13-Cyclobutyl Epothilones |
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