Molecular docking studies of the interaction between propargylic enol ethers and human DNA topoisomerase IIα

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Silveira-Dorta, Gaston¹  Sousa, Ines J.²  Rios-Luci, Carla^1,3  Martin, Victor S.¹  Fernandes, Miguel X.^1,2  Padron, Jose M.¹ 

[1] Univ La Laguna, Ctr Invest Biomed Canarias CIBICAN, Inst Univ Bioorgan Antonio Gonzalez IUBO AG, San Cristobal la Laguna 38206, Spain

[2] Univ Madeira, Ctr Quim Madeira, P-9000390 Funchal, Portugal

[3] Univ Salamanca, Ctr Invest Canc, IBMCC CSIC, Salamanca 37007, Spain

关键词: Antitumor agents;    Chirality;    Docking studies;    Enzyme inhibitors;    Topoisomerase II alpha;   

DOI  :  10.1016/j.bmcl.2013.07.055

来源: Elsevier

【 摘 要 】

Having identified a novel human DNA topoisomerase II alpha (TOP2) catalytic inhibitor from a small and structure-focused library of propargylic enol ethers, we decided to analyze if the chirality of these compounds plays a determinant role in their antiproliferative activity. In this study, we describe for the first time the synthesis of the corresponding enantiomers and the biological evaluation against a panel of representative human solid tumor cell lines. Experimental results show that chirality does not influence the reported antiproliferative activity of these compounds. Docking studies of corresponding enantiomers against TOP2 reinforce the finding that the biological effect is not chiral-dependent and that these family of compounds seem to act as TOP2 catalytic inhibitors. (C) 2013 Elsevier Ltd. All rights reserved.

【 授权许可】

Free