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JS-1, a novel isoquinoline alkaloid with antimicrobial activity isolated from Streptomyces sp. 8812

Jolanta Solecka 1Aleksandra M. Rajnisz 1Wojciech Bocian 3Lech Kozerski 2,3

1. National Institute of Public Health-National Institute of Hygiene, Warszawa 00-791, Poland
2. Polish Academy of Science, Institute of Organic Chemistry, Kasprzaka 44/52, Warszawa 01-224, Poland
3. National Medicines Institut (NIL), Chełmska 30/34, Warsaw 00-725, Poland

Abstract

The increasing bacterial resistance to antibiotics is at present a great therapeutic problem. Multi-resistant pathogenic bacteria occur more and more frequently. Hence, there is a necessity for the discovery of new classes of antibiotics for the treatment of drug resistant bacterial infections. One of the solution of this problem, apart from combinatorial chemistry, rational drug design and computer assisted design technology involves screening for microorganisms producing novel antimicrobial drugs. Streptomycetes are well known producers of antibiotics and other bioactive metabolites. Enzymes and structures taking part in cell wall biosynthesis have proved to be excellent targets for antibacterial agents because the cell wall pathway is conserved among bacterial pathogens and is absent from mammalian cells. β-lactam antibiotics are the most important class of DD-peptidases/penicillin-binding proteins inhibitors and antimicrobial agents. Moreover, are known only γ-lactams and pyrazolidinones led to moderate antimicrobial activity through the inhibition of the DD-peptidases. In our screening program for novel inhibitors of DD-peptidases from microbial secondary metabolits from our collection of streptomycetes strains, we used DD-peptidase 64-575 II [1]. The novel compound with antibacterial activity JS-1, DD-peptidases inhibitor, member of isoquinoline alkaloids was isolated from the culture broth of Streptomyces sp. 8812. It was purified by acetone protein precipitation from the culture supernatant, used of anion exchanging resin column and RP HPLC with C18 modified column. The molecular formula C10H9NO4 was deduced from HRESI-MS and NMR data. JS-1 is inhibitor of exocellular DD-peptidases 64-575 II from Saccharopolyspora erythraea 64-575 II, R61 from Streptomyces R61 and R39 from Actinomadura R39. JS-1 exhibited significant activity against the Gram-negative bacteria [2].

[1] Solecka J, Kurzatkowski W. Affinity of exocellular DD-carboxypeptidase/transpeptidase from Saccharopolyspora erythraea PZH 64-575 to beta-lactam compounds. Med Dosw Mikrobiol 51: 151–165 (1999)
[2] Solecka J, Kozerski L. Pat. Appl Nr P 383211 (2007)

Acknowledgement: This work was supported by network "Synthesis, structure and therapeutic properties of compounds and organic substances", Poland. We are grateful to Prof. Jean-Maria Ghuysen (Centre for Protein Engineering and Laboratoire d’Enzymologie, Université de Liège, Belgium) for kindly providing us with DD-peptidases R61 and R39.

 

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Submitted: 2008-03-12 15:50
Revised:   2009-06-07 00:48