Isolation of novel anti-TB cyclohexapeptides from actinomycetes
Thirty-five thousand actinomycete extracts were screened for anti-TB activity, followed by C 18 cartridge fractionation of 37 prioritized extracts. Based on MICs against replicating and non-replicating M. tuberculosis (Mtb), and IC 50 s against Vero cells to generate selectivity indices, seven fract...
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Published in | Planta Medica |
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Main Authors | , , , , , , , , , , |
Format | Conference Proceeding |
Language | English |
Published |
19.07.2012
|
Online Access | Get full text |
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Summary: | Thirty-five thousand actinomycete extracts were screened for anti-TB activity, followed by C
18
cartridge fractionation of 37 prioritized extracts. Based on MICs against replicating and non-replicating M. tuberculosis (Mtb), and IC
50
s against Vero cells to generate selectivity indices, seven fractions were selected for further separation. ECUM14046, a Streptomyces hygroscopicus strain, when cultured in GSS media and extracted with ethyl acetate, yielded a fraction with potent anti-TB activity. This fraction had a well-defined thin layer chromatography (TLC) profile and was therefore further fractionated using preparative HPLC. The molecular formulas of two purified components, designated as hytramycin-V and hytramycin-I, were determined by high-resolution mass spectrometry (ESI-IT-TOF) as C
30
H
51
N
9
O
6
and C
31
H
53
N
9
O
6
, resp. Structure elucidation by 1D/2D NMR revealed both to be cyclohexapeptides with three unusual piperazic acid moieties. The MICs against replicating and especially non-replicating Mtb fall into the range of existing anti-TB drugs, such as streptomycin and capreomycin, and were maintained against Mtb strains that represent the major global clades, as well as H
37
Rv-isogenic strains that are resistant to individual clinical anti-TB drugs. |
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ISSN: | 0032-0943 1439-0221 |
DOI: | 10.1055/s-0032-1320753 |