Novel Screen Methodologies for Identification of New Microbial Metabolites
101
O
HO~OH
OH 0 OH ~0
i
OH
OH
H2
0
O
_1/.,,,,OH
- . , ......
/COCH3
HN
OH
HO
N
HO
CO2H
CH2OH
3
4
Fig. 7. Structures of the topoisomerase I-mediated DNA cleavage inducer UCE6, 1, the
topoisomerase I inhibitor TAN-1518 A, 2, the topoisomerase II inhibitor UCT4B, 3 (Sect. 4.2.2) and
the N-acety-13-D-glucosaminadase inhibitor nagstatin, 4 (Sect. 4.2.5)
BE-22179, an unusual cyclic depsipeptide containing two thioester linkages
produced by a Streptomyces sp., was discovered in a screening programme for
Topo II inhibitors using a similar assay [122]. BE-22179 inhibited murine
leukaemia cell Topo II relaxation of supercoiled pBR322 plasmid DNA, but did
not inhibit Topo I from the same source. The compound was active against
P388, L1210 (murine leukaemia) and MKN-45 (human stomach adenocarcinoma) cell lines. BE-22179 prolonged survival time of mice transplanted with
L1210 leukaemic cells at doses lower than those at which toxicity was observed.
101
O
HO~OH
OH 0 OH ~0
i
OH
OH
H2
0
O
_1/.,,,,OH
- . , ......
/COCH3
HN
OH
HO
N
HO
CO2H
CH2OH
3
4
Fig. 7. Structures of the topoisomerase I-mediated DNA cleavage inducer UCE6, 1, the
topoisomerase I inhibitor TAN-1518 A, 2, the topoisomerase II inhibitor UCT4B, 3 (Sect. 4.2.2) and
the N-acety-13-D-glucosaminadase inhibitor nagstatin, 4 (Sect. 4.2.5)
BE-22179, an unusual cyclic depsipeptide containing two thioester linkages
produced by a Streptomyces sp., was discovered in a screening programme for
Topo II inhibitors using a similar assay [122]. BE-22179 inhibited murine
leukaemia cell Topo II relaxation of supercoiled pBR322 plasmid DNA, but did
not inhibit Topo I from the same source. The compound was active against
P388, L1210 (murine leukaemia) and MKN-45 (human stomach adenocarcinoma) cell lines. BE-22179 prolonged survival time of mice transplanted with
L1210 leukaemic cells at doses lower than those at which toxicity was observed.