Thiocolchicine-podophyllotoxin conjugates: dynamic libraries based on disulfide exchange reaction.
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.
Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, 20133 Milan, Italy.
Bruno
B
Danieli
Alessandra
A
Giardini
Giordano
G
Lesma
Daniele
D
Passarella
Bruno
B
Peretto
Alessandro
A
Sacchetti
Alessandra
A
Silvani
Graziella
G
Pratesi
Franco
F
Zunino
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003078:Colchicine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004220:Disulfides / Q000737:chemistry* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D008968:Molecular Conformation; D011034:Podophyllotoxin / Q000737:chemistry* / Q000494:pharmacology; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism
D004220:Disulfides; C014856:thiocholchicine; D011034:Podophyllotoxin; D003078:Colchicine