TY - JOUR
T1 - Herbimycins D-F, ansamycin analogues from streptomyce s sp. RM-7-15
AU - Shaaban, Khaled A.
AU - Wang, Xiachang
AU - Elshahawi, Sherif I.
AU - Ponomareva, Larissa V.
AU - Sunkara, Manjula
AU - Copley, Gregory C.
AU - Hower, James C.
AU - Morris, Andrew J.
AU - Kharel, Madan K.
AU - Thorson, Jon S.
PY - 2013/9/27
Y1 - 2013/9/27
N2 - 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.
AB - 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.
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U2 - 10.1021/np400308w
DO - 10.1021/np400308w
M3 - Article
C2 - 23947794
AN - SCOPUS:84885053387
SN - 0163-3864
VL - 76
SP - 1619
EP - 1626
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 9
ER -