Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents
Journal
European Journal of Medicinal Chemistry
Journal Volume
69
Pages
278-293
Date Issued
2013
Author(s)
Chen T.-C.
Yu D.-S.
Huang K.-F.
Fu Y.-C.
Lee C.-C.
Chen C.-L.
Huang F.-C.
Hsieh H.-H.
Huang H.-S.
Abstract
By using fragment-based design strategies, a series of 2-thio-substituted anthra[1,2-d]imidazole-6,11-diones were synthesized and evaluated for hTERT repressing activities, cell proliferations, and NCI 60-cell panel assay. Compounds 2, 3, 4, 11, 15 and 35 were selected by the NCI and 3, 4, 11 and 15 represent the GI50, TGI and LC50, respectively. Among them, all were moderate selectivity toward leukemia cancer except for 4 exhibited distinctive selectivity of CNS and renal cancer with 7.403 and 6.475. The overall of test compounds exhibited different cytostatic and cytotoxic activities for further developing potential application as anticancer drugs. ? 2013 Published by Elsevier Masson SAS. All rights reserved.
Subjects
Anthra 12-dimidazole-611-dione; Cytostatic and cytotoxic activities; NCI 60-cell panel assay; Selectivity ratio
SDGs
Other Subjects
2 ((2 (pyrrolidin 1 yl)ethyl)thio) 1h anthra[1,2 d] imidazole 6,11 dione; 2 ((3 (dimethylamino)propyl)thio) 1h anthra[1,2 d] imidazole 6,11 dione; 2 (ethylthio) 1h anthra[1,2 d]imidazole 6,11 dione; 2 (propylthio) 1h anthra[1,2 d]imidazole 6,11 dione; 2 mercapto 1(3)h anthra[1,2 d] imidazole 6,11 dion; 2 thioxo 2,3 dihydro 1h anthra[1,2 d]imidazole 6,11 dione; antineoplastic agent; unclassified drug; antineoplastic activity; article; breast cancer; cancer cell culture; cell proliferation; cell viability; central nervous system tumor; colon cancer; controlled study; cytostasis; cytotoxicity; drug design; drug structure; drug synthesis; gene repression; human; human cell; human cell culture; in vitro study; kidney cancer; LC 50; leukemia; lung non small cell cancer; melanoma; ovary cancer; prostate cancer; substitution reaction; Anthra[1,2-d]imidazole-6,11-dione; Cytostatic and cytotoxic activities; NCI 60-cell panel assay; Selectivity ratio; Anthraquinones; Antineoplastic Agents; Benzimidazoles; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Heterocyclic Compounds with 4 or More Rings; Humans; Molecular Structure; Structure-Activity Relationship; Telomerase
Type
journal article