Sinefungin VA and dehydrosinefungin V, new antitrypanosomal antibiotics produced by Streptomyces sp. K05-0178.
Two new nucleotide antibiotics, named sinefungin VA and dehydrosinefungin V, were separated by cation exchange column chromatography and purified by HPLC from the culture broth of Streptomyces sp. K05-0178, together with the known antibiotics, sinefungin, dehydrosinefungin and KSA-9342. The structures of the two novel sinefungin analogs were elucidated by spectroscopic studies, including various NMR and advanced peptide chemical methods. Sinefungin VA consists of adenosine and ornithylvalylalanine, whereas dehydrosinefungin V consists of 4',5'-dehydroadenosine and ornithylvaline. Sinefungin VA showed potent antitrypanosomal activity with an IC(50) value of 0.0026 μg ml(-1) in vitro without cytotoxicity against MRC-5 cells. Dehydrosinefungin V showed moderate antitrypanosomal activity (IC(50)=0.15 μg ml(-1)).
Niitsuma
Megumi
M
Research Center for Tropical Diseases, Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
Hashida
Junko
J
Iwatsuki
Masato
M
Mori
Mihoko
M
Ishiyama
Aki
A
Namatame
Miyuki
M
Nishihara-Tsukashima
Aki
A
Matsumoto
Atsuko
A
Takahashi
Yoko
Y
Yamada
Haruki
H
Otoguro
Kazuhiko
K
Shiomi
Kazuro
K
Omura
Satoshi
S
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D002460:Cell Line; D002852:Chromatography, Ion Exchange / Q000379:methods; D005285:Fermentation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013057:Spectrum Analysis / Q000379:methods; D013302:Streptomyces / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D014344:Trypanocidal Agents; C554558:dehydrosinefungin V; C554557:sinefungin VA; D000241:Adenosine