Antifungal actinomycete metabolites discovered in a differential cell-based screening using a recombinant TOPO1 deletion mutant strain

Citation
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
Citations number
14
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ARCHIV DER PHARMAZIE
ISSN journal
0365-6233 → ACNP
Volume
334
Issue
5
Year of publication
2001
Pages
143 - 147
Database
ISI
SICI code
0365-6233(200105)334:5<143:AAMDIA>2.0.ZU;2-4
Abstract
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.