title: Synthesis and Biological Evaluation of Novel Epothilone B Side Chain Analogues.
abstract: The design, synthesis, and biological evaluation of a series of epothilone analogues with novel side chains equipped with an amino group are described. Their design facilitates potential conjugation to selective drug delivery systems such as antibodies. Their synthesis proceeded efficiently via Stille coupling of a readily available vinyl iodide and heterocyclic stannanes. Cytotoxicity studies and tubulin binding assays revealed two of these analogues to be more potent than epothilones A-D and the anticancer agent ixabepilone, currently in clinical use.
authors.affiliation: Department of Chemistry, Rice University, 6100 Main Street, Houston, TX, 77005, USA. kcn@rice.edu.
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.affiliation: Department of Chemistry, Rice University, 6100 Main Street, Houston, TX, 77005, USA.|Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Rhoades
authors.affiliation: Department of Chemistry, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Rice University, 6100 Main Street, Houston, TX, 77005, USA.|Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Totokotsopoulos
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
authors.forename: Ruoli
authors.initials: R
authors.lastname: Bai
authors.affiliation: Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
authors.forename: Ernest
authors.initials: E
authors.lastname: Hamel
mesh_terms: D000906:Antibodies / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D011485:Protein Binding; D013329:Structure-Activity Relationship; D017971:Tin Compounds / Q000737:chemistry; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004337:Drug Carriers; D034261:Epothilones; D017971:Tin Compounds; D014404:Tubulin; D014753:Vinyl Compounds; C569210:vinyl iodide; C031525:stannane; C093788:epothilone B
keywords: antibody-drug conjugates; anticancer agents; epothilones; organic synthesis; tubulin binding agents