Structure and activity of lobophorins from a turrid mollusk-associated Streptomyces sp.
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.
Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA.
Zhenjian
Z
Lin
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Michael
M
Koch
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Christopher D
CD
Pond
Marine Science Institute, University of the Philippines Diliman, Quezon City, Philippines.
Gaiselle
G
Mabeza
Marine Science Institute, University of the Philippines Diliman, Quezon City, Philippines.
Romell A
RA
Seronay
Marine Science Institute, University of the Philippines Diliman, Quezon City, Philippines.
Gisela P
GP
Concepcion
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT, USA.
Louis R
LR
Barrows
Department of Biology, University of Utah, Salt Lake City, UT, USA.
Baldomero M
BM
Olivera
1] Department of Medicinal Chemistry, L.S. Skaggs Pharmacy Institute, University of Utah, Salt Lake City, UT, USA [2] Department of Biology, University of Utah, Salt Lake City, UT, USA.
Eric W
EW
Schmidt
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D008974:Mollusca / Q000382:microbiology*; D061065:Polyketides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013057:Spectrum Analysis; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018942:Macrolides; D061065:Polyketides