Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA topoisomerase I inhibitory properties.

Authors :: Lee CC
Chang DM
Huang KF
Chen CL
Chen TC
Lo Y
Guh JH
Huang HS
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Nov 15; Vol. 21 (22), pp. 7125-33. Date of Electronic Publication: 2013 Sep 13.
Publication Year :: 2013
Abstract: A series of 2,7-diamidofluorenones were designed, synthesized, and screened by SRB assay. Some synthesized compounds exhibited antitumor activities in submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j) were also selected by NCI screening system and 3c (GI50=1.66 μM) appeared to be the most active agent of this series. Furthermore, 3c attenuated topoisomerase I-mediated DNA relaxation at low micromolar concentrations. These results indicated that fluorenones have potential to be further developed into anticancer drugs.<br /> (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Subjects :: Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Proliferation drug effects
DNA Topoisomerases, Type I metabolism
Humans
Structure-Activity Relationship
Tilorone chemistry
Tilorone pharmacology
Topoisomerase I Inhibitors chemistry
Antineoplastic Agents chemical synthesis
Antineoplastic Agents pharmacology
DNA Topoisomerases, Type I chemistry
Drug Design
Tilorone analogs & derivatives
Topoisomerase I Inhibitors chemical synthesis
Topoisomerase I Inhibitors pharmacology

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