| Combined Muta- and Semisynthesis: A Powerful Synthetic Hybrid Approach to Access Target Specific Antitumor Agents Based on Ansamitocin P3. | |
| | |
MedLine Citation:
|
PMID: 22170289 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Access of four new tumor specific folic acid/ansamitocin conjugates is reported that relies on a synthetic strategy based on the combination of mutasynthesis and semisynthesis. Two bromo-ansamitocin derivatives were prepared by mutasynthesis or by a modified fermentation protocol, respectively, that served as starting point for the semisynthetic introduction of an allyl amine linker under Stille conditions. A sequence of standard coupling steps introduced the pteroic acid/glutamic acid/cysteine unit to the modified ansamitocins. All new derivatives, including those that are expected to be generated after internalization of the folic acid/ansamitocin conjugates into the cancer cell and reductive cleavage of the disulfide linkage showed good to strong antiproliferative activity (IC(50) <10 nM) for different cancer cell lines. Finally, the four conjugates were exposed to two cancer cell lines [cervix carcinoma, KB-3-1 (FR+) and lung carcinoma, A-459 (FR-)], the latter devoid of the membrane-bound folic acid receptor (FR-). All four conjugates showed strong antiproliferative activity for the FR+ cancer cell line but were inactive against the FR- cell line. The synthetic strategy pursued is based on the combination of mutasynthesis and semisynthesis and proved to be powerful for accessing new ansamitocin derivatives that are difficult to prepare by total synthesis. |
| | |
Authors:
|
Florian Taft; Kirsten Harmrolfs; Irinia Nickeleit; Anja Heutling; Miriam Kiene; Nisar Malek; Florenz Sasse; Andreas Kirschning |
Related Documents
:
|
16650969 - Effect of n-3 and n-6 polyunsaturated fatty acids on lymphocyte proliferation, interleu... 14972629 - Cutin and suberin monomers are membrane perturbants. 11076799 - Lung function, permeability, and surfactant composition in oleic acid-induced acute lun... 3482349 - Alteration of membrane phospholipids in hypertrophied rat salivary glands induced by ch... 11058809 - Effect of nucleoside analogues and oligonucleotides on hydrolysis of liposomal phosphol... 8110809 - In vitro oxygenation of soybean biomembranes by lipoxygenase-2. 20442319 - Oxidation of intramyocellular lipids is dependent on mitochondrial function and the ava... 838709 - Revised amino acid sequence of qbeta coat protein between positions 1 and 60. 21187189 - Effects of alpha-lipoic acid on body weight in obese subjects. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-12-14 |
Journal Detail:
|
Title: Chemistry (Weinheim an der Bergstrasse, Germany) Volume: - ISSN: 1521-3765 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9513783 Medline TA: Chemistry Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
|
Institut für Organische Chemie und Biomolekulares Wirkstoffzentrum (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover (Germany), Fax: (+49) 511-762-3011. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Translational genetic approaches to substance use disorders: bridging the gap between mice and human...
Next Document: The Management of Patients with Atrial Fibrillation and Dronedarone's Place in Therapy.