Document Detail


Veraguamides A-G, cyclic hexadepsipeptides from a dolastatin 16-producing cyanobacterium Symploca cf. hydnoides from Guam.
MedLine Citation:
PMID:  21446699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytotoxicity-directed purification of a Symploca cf. hydnoides sample from Cetti Bay, Guam, afforded seven new cyclic depsipeptides, veraguamides A-G (1-7), together with the known compound dolastatin 16. The planar structures of 1-7 were elucidated using NMR and MS experiments, while enantioselective HPLC and Mosher's analysis of acid and base hydrolysates, respectively, were utilized to assign the absolute configurations of the stereocenters. Veraguamides A-G (1-7) are characterized by the presence of an invariant proline residue, multiple N-methylated amino acids, an α-hydroxy acid, and a C8-polyketide-derived β-hydroxy acid moiety with a characteristic terminus as either an alkynyl bromide, alkyne, or vinyl group. These compounds and a semisynthetic analogue (8) showed moderate to weak cytotoxic activity against HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cell lines. Preliminary structure-activity relationship analysis identified several sensitive positions in the veraguamide scaffold that affect the cytotoxic activity of this compound class. Dolastatin 16 showed only weak cytotoxic activity on both cell lines tested. The complete stereostructure of dolastatin 16 was proposed for the first time through degradation followed by a combination of advanced Marfey's analysis and modified Mosher's analysis using phenylglycine methyl ester as a chiral anisotropic reagent.
Authors:
Lilibeth A Salvador; Jason S Biggs; Valerie J Paul; Hendrik Luesch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-29
Journal Detail:
Title:  Journal of natural products     Volume:  74     ISSN:  1520-6025     ISO Abbreviation:  J. Nat. Prod.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-27     Completed Date:  2011-08-17     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7906882     Medline TA:  J Nat Prod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  917-27     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  isolation & purification*,  pharmacology
Cyanobacteria / chemistry*
Depsipeptides / chemistry,  isolation & purification*,  pharmacology
Drug Screening Assays, Antitumor
Female
Guam
HT29 Cells
HeLa Cells
Humans
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Structure-Activity Relationship
Grant Support
ID/Acronym/Agency:
P41 GM086210/GM/NIGMS NIH HHS; P41 GM086210-01S1/GM/NIGMS NIH HHS; P41 GM086210-02/GM/NIGMS NIH HHS; P41 GM086210-03/GM/NIGMS NIH HHS; P41GM086210/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Depsipeptides; 0/dolastatin 16; 0/veraguamide A
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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