Ring fusion strategy for the synthesis of anthra[2,3-d ]oxazole-2-thione-5,10-dione homologues as DNA topoisomerase inhibitors and as antitumor agents
Journal
European Journal of Medicinal Chemistry
Journal Volume
87
Pages
30-38
Date Issued
2014
Author(s)
Abstract
The efficient synthesis of mono-substituted anthraquinones and ring fusion into anthra[2,3-d]oxazole-2-thione-5,10-dione derivatives were developed, and all the compounds were tested for their cytotoxicity against PC-3 cancer cell lines. Compounds 8, 14, 17 and 23 were selected by the NCI and 12, 17 and 19 were evaluated for topoisomerase I-mediated DNA relaxation. Among them, 17 appeared to be the most active compound of this series and not only showed higher inhibition when indicated from the low IC50values against PC-3 cancer cell line but also attenuated the in vitro topoisomerase I-mediated DNA relaxation at low micromolar concentrations. All test compounds exhibited different cytostatic and cytotoxic activities for further developing potential anticancer drugs. ? 2014 Elsevier Masson SAS.
Subjects
cell panel assay; mediated DNA relaxation NCI 60; Topoisomerase I
SDGs
Other Subjects
2 (3 chloropropionamido) 3 hydroxy anthraquinone; 2 (butylthio)anthra[2,3 d]oxazole 5,10 dione; 2 (chloroacetamido) 3 hydroxy anthraquinone; 2 (ethylthio)anthra[2,3 d]oxazole 5,10 dione; 2 (methylthio)anthra[2,3 d]oxazole 5,10 dione; 2 (propylthio)anthra[2,3 d]oxazole 5,10 dione; 2 [(2 fluorobenzyl)thio]anthra[2,3 d]oxazole 5,10 dione; 2 [(2 morpholinoethyl)thio]anthra[2,3 d]oxazole 5,10 dione; 2 [(4 fluorobenzyl)thio]anthra[2,3 d]oxazole 5,10 dione; 2 [2 (diethylamino)acetamido] 3 hydroxy anthraquinone; 2 [2 (n morpholin)acetamido] 3 hydroxy anthraquinone; 2 [2 (n piperidin)acetamido] 3 hydroxy anthraquinone; 2 [2 (pyrrolidinyl)acetamido] 3 hydroxy anthraquinone; 2 [3 (diethylamino)propionamido] 3 hydroxy anthraquinone; 2 [3 (n morpholin)propionamido] 3 hydroxy anthraquinone; 2 [3 (n piperidin)propionamido] 3 hydroxy anthraquinone; 2 [3 (n pyrrolidinyl)propionamido] 3 hydroxy anthraquinone; 2 [[2 (piperidin 1 yl)ethyl]thio]anthra[2,3 d]oxazole 5,10 dione; 2 [[3 (dimethylamino)propyl]thio]anthra[2,3 d]oxazole 5,10 dione; 2 [[3 (piperidin 1 yl)propyl]thio]anthra[2,3 d]oxazole 5,10 dione; anthraquinone derivative; anthra[2,3 b][1,4]oxazine 3,6,11 trione; anthra[2,3 d]oxazole 2 thione 5,10 dione; anthra[2,3 d]oxazole 2 thione 5,10 dione derivative; camptothecin; cytostatic agent; cytotoxic agent; DNA topoisomerase inhibitor; oxazole derivative; unclassified drug; unindexed drug; anthraquinone derivative; antineoplastic agent; DNA topoisomerase; DNA topoisomerase inhibitor; oxazole derivative; antineoplastic activity; antiproliferative activity; Article; cancer inhibition; concentration response; controlled study; cytostasis; drug cytotoxicity; drug potency; drug screening; drug synthesis; human; human cell; IC50; in vitro study; male; prostate cancer cell line; cell proliferation; chemical structure; chemistry; dose response; drug design; drug effects; pathology; Prostatic Neoplasms; structure activity relation; synthesis; tumor cell culture; Anthraquinones; Antineoplastic Agents; Cell Proliferation; DNA Topoisomerases, Type I; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Male; Molecular Structure; Oxazoles; Prostatic Neoplasms; Structure-Activity Relationship; Topoisomerase Inhibitors; Tumor Cells, Cultured
Type
journal article