Document Detail

Conjugation of quinones with natural polyamines: towards an expanded anti-trypanosomatid profile.
MedLine Citation:
PMID:  23153330     Owner:  NLM     Status:  Publisher    
A combinatorial library of quinone-polyamine conjugates designed to optimize the anti-trypanosomatid profile of hit compounds 1 and 2 has been prepared by a solid phase approach. The conjugates were evaluated against three most important human trypanosomatid pathogens (T. b. rhodesiense, T. cruzi, and L. donovani) and several showed promising activity. A subset also inhibited trypanothione reductase in vitro and induced oxidase activity of the enzyme. A highly potent analogue (7) was identified with activity against T. brucei as low as 70 nM and a selectivity index of 72. Interestingly, the presence of a cadaverine tail confers to 7 the ability to target mitochondrial function in Leishmania. In fact, in L. donovani promastigotes we verified for 7 a decrease of cytoplasmic ATP and mitochondrial potential. Therefore, the current results support the suitability of the conjugation approach for the development of novel polyamine-conjugates with enhanced therapeutic potential.
Federica Lizzi; Giacomo Veronesi; Federica Belluti; Christian Bergamini; Almudena Lopez-Sanchez; Marcel Kaiser; Reto Brun; R Luise Krauth-Siegel; Dennis Hall; Luis Rivas; Maria Laura Bolognesi
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-16
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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