Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA topoisomerase i inhibitory properties
Journal
Bioorganic and Medicinal Chemistry
Journal Volume
21
Journal Issue
22
Pages
7125-7133
Date Issued
2013
Author(s)
Lee C.-C.
Chang D.-M.
Huang K.-F.
Chen C.-L.
Chen T.-C.
Lo Y.
JIH-HWA GUH
Huang H.-S.
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. ? 2013 Elsevier Ltd. All rights reserved.
Subjects
Fluorenones; NCI 60-cell panel assay; Tilorone; Topoisomerase I
SDGs
Other Subjects
2,7 bis(3 chloropropionamido) 9 fluorenone; 2,7 bis(chloroacetamido) 9 fluorenone; 2,7 bis[2 (butylamino)acetamido] 9 fluorenone; 2,7 bis[2 (ethylthio)acetamido] 9 fluorenone; 2,7 bis[2 (isobutylamino)acetamido] 9 fluorenone; 2,7 bis[2 (isopropylamino)acetamido] 9 fluorenone; 2,7 bis[2 (isopropylthio)acetamido] 9 fluorenone; 2,7 bis[2 (morpholine)acetamido] 9 fluorenone; 2,7 bis[2 (n methylpiperazino)acetamido] 9 fluorenone; 2,7 bis[2 (piperidino)acetamido] 9 fluorenone; 2,7 bis[2 (propylamino)acetamido] 9 fluorenone; 2,7 bis[2 (propylthio)acetamido] 9 fluorenone; 2,7 bis[2 (pyrrolidino)acetamido] 9 fluorenone; 2,7 bis[2 [(2 hydroxyethyl)amino]acetamido] 9 fluorenone; 2,7 bis[2 [(2 hydroxyethyl)thio]acetamido] 9 fluorenone; 2,7 bis[3 (butylamino)propionamido] 9 fluorenone; 2,7 bis[3 (ethylamino)propionamido] 9 fluorenone; 2,7 bis[3 (isobutylamino)propionamido] 9 fluorenone; 2,7 bis[3 (isopropylamino)propionamido] 9 fluorenone; 2,7 bis[3 (propylamino)propionamido] 9 fluorenone; 2,7 diamidofluorenone; 2,7 diamidofluorenone derivative; 2,7 diamino 9 fluorenone; anthraquinone derivative; antineoplastic agent; camptothecin; DNA topoisomerase inhibitor; fluorenone derivative; nsc 746364; nsc 763959; nsc 763960; nsc 763961; nsc 763962; nsc 763963; nsc 763964; nsc 763973; nsc 763974; nsc 763975; nsc 765593; unclassified drug; unindexed drug; antiproliferative activity; article; cancer cell; cancer inhibition; concentration response; controlled study; cytostasis; drug cytotoxicity; drug design; drug screening; drug synthesis; human; human cell; structure activity relation; Fluorenones; NCI 60-cell panel assay; Tilorone; Topoisomerase I; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA Topoisomerases, Type I; Drug Design; Humans; Structure-Activity Relationship; Tilorone; Topoisomerase I Inhibitors
Type
journal article