Histone deacetylase and microtubules as targets for the synthesis of releasable conjugate compounds

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:19

Article

Passarella, Daniele¹  Comi, Daniela¹  Vanossi, Andrea¹  Paganini, Gianfranco¹  Colombo, Francesco¹  Ferrante, Luca¹  Zuco, Valentina²  Danieli, Bruno¹  Zunino, Franco² 

[1] Univ Milan, Dipartimento Chim Organ & Ind, I-20122 Milan, Italy

[2] Fdn IRCCS Ist Nazl Studio & Cura Tumori, I-20133 Milan, Italy

关键词: HDAC inhibitors;    Tubulin binders;    Releasable conjugate compounds;    Disulfide bond;    Anticancer compounds;   

DOI  :  10.1016/j.bmcl.2009.09.075

来源: Elsevier

【 摘 要 】

Design and synthesis of an HDAC inhibitor and its merger with three tubulin binders to create releasable conjugate compounds is described. The biological evaluation includes: (a) in vitro reactivity with glutathione, (b) antiproliferative activity, (c) cell cycle analysis and (d) quantification of protein acetylation. The cellular pharmacology study indicated that the HDAC-inhibitor-drug conjugates retained antimitotic and proapoptotic activity with a reduced potency. (C) 2009 Elsevier Ltd. All rights reserved.

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