Thiocolchicine−Podophyllotoxin Conjugates: Dynamic Libraries Based on Disulfide Exchange Reaction
The Journal of Organic Chemistry2006Vol. 71(7), pp. 2848–2853
Citations Over TimeTop 10% of 2006 papers
Bruno Danieli, Alessandra Giardini, Giordano Lesma, Daniele Passarella, Bruno Peretto, Alessandro Sacchetti, Alessandra Silvani, Graziella Pratesi, Franco Zunino
Abstract
A dynamic combinatorial library of thiocolchicine-podophyllotoxin derivatives based on the disulfide bond exchange reaction is described. The influence of a biological target on the composition of the reaction mixture has been demonstrated. Use of high-resolution ESI mass spectrometry to evaluate the composition of the mixture shows promise for the design of new large libraries. The biological evaluation demonstrates that formation of a divalent compound affords a new chemical entity whose biological activity is not merely the sum of the single ligands activities, thus reflecting a different interaction with the biological target.
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