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1.
J Antibiot (Tokyo) ; 67(1): 121-6, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24220110

ABSTRACT

A novel lumun-lumun sampling methodology was used to obtain a large diversity of micromollusks, including the new species Lienardia totopotens. In turn, from L. totopotens we cultivated a Streptomyces sp. strain that contained new and known spirotetronate polyketides, lobophorins (1-5). The structures were elucidated using spectroscopy, and the compounds were evaluated for cytotoxicity to human cells and activity against Mycobacterium tuberculosis, Bacillus subtilis, Pseudomonas aeruginosa and Burkholderia cepacia. Compounds 2-5 showed varying degrees of activity against human cells, M. tuberculosis and B. subtilis in the low µM to mid nM range but were inactive against the other strains, while 1 lacking digitoxose was inactive. Very slight structural changes in 2-5 led to varying antibacterial:cytotoxicity ratios, providing a possible basis to synthesize more selective derivatives.


Subject(s)
Macrolides/pharmacology , Mollusca/microbiology , Polyketides/pharmacology , Streptomyces/chemistry , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Bacteria/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Macrolides/chemistry , Macrolides/isolation & purification , Microbial Sensitivity Tests , Molecular Sequence Data , Polyketides/chemistry , Polyketides/isolation & purification , Spectrum Analysis , Streptomyces/genetics , Streptomyces/isolation & purification , Structure-Activity Relationship
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