Herbimycins D-F, ansamycin analogues from Streptomyces sp. RM-7-15.
Bacterial strains belonging to the class actinomycetes were isolated from the soil near a thermal vent of the Ruth Mullins coal fire (Appalachian Mountains of eastern Kentucky). High-resolution electrospray ionization mass spectrometry and ultraviolet absorption profiles of metabolites from one of the isolates (Streptomyces sp. RM-7-15) revealed the presence of a unique set of metabolites ultimately determined to be herbimycins D-F (1-3). In addition, herbimycin A (4), dihydroherbimycin A (TAN 420E) (7), and the structurally distinct antibiotic bicycylomycin were isolated from the crude extract of Streptomyces sp. RM-7-15. Herbimycins A and D-F (1-3) displayed comparable binding affinities to the Hsp90α. While the new analogues were found to be inactive in cancer cell cytotoxicity and antimicrobial assays, they may offer new insights in the context of nontoxic ansamycin-based Hsp90 inhibitors for the treatment of neurodegenerative disease.
Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536-0596, United States.
Khaled A
KA
Shaaban
Xiachang
X
Wang
Sherif I
SI
Elshahawi
Larissa V
LV
Ponomareva
Manjula
M
Sunkara
Gregory C
GC
Copley
James C
JC
Hower
Andrew J
AJ
Morris
Madan K
MK
Kharel
Jon S
JS
Thorson
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D019906:Nuclear Magnetic Resonance, Biomolecular; D017828:Rifabutin / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D019779:Salmonella enterica / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry
D000900:Anti-Bacterial Agents; D018841:HSP90 Heat-Shock Proteins; C584725:herbimycin D; C584726:herbimycin E; C584727:herbimycin F; D017828:Rifabutin; C020754:herbimycin