M. Stadler et al., Antifungal actinomycete metabolites discovered in a differential cell-based screening using a recombinant TOPO1 deletion mutant strain, ARCH PHARM, 334(5), 2001, pp. 143-147
In the course of a natural product screening for inhibitors of fungal topoi
somerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS
1465 exhibited promising activities. Bioguided fractionation of the culture
broth by preparative HPLC methods yielded the collismycins A (1) and B (2)
as active principles of strain WS 1410. Out of the mycelial extracts of st
rain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3
) and cyclo-nonactic acid (5) and the structurally related but inactive hom
ononactic acid (4), were isolated. Both collismycin isomers inhibited the r
ecombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in
a non-specific manner with an MIC in the range of 2 mug/ml. The novel cyclo
-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivit
y towards the wild type strain (MIC = 2 mug/ml as compared to 10 mug/ml for
the deletion mutant). All compounds obviously address a target other than
TOW 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme as
say.