Ring fusion strategy for synthesis and lead optimization of sulfur-substituted anthra[1,2-c[[1,2,5]thiadiazole-6,11-dione derivatives as promising scaffold of antitumor agents
Journal
European Journal of Medicinal Chemistry
Journal Volume
102
Pages
661-676
Date Issued
2015
Author(s)
Abstract
A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents. ? 2015 Elsevier Masson SAS.
Subjects
Anthra[1 2-c][1 2 5]thiadiazole-6 11-dione; Apoptosis; NCI 60-cell panel assay; SRB assay; Thiadiazoles
SDGs
Other Subjects
4 (2 bromophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2 chlorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2 ethylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2 fluorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2 isopropylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2,4 difluorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2,4 dimethylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2,5 dichlorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (2,6 dimethylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3 bromophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3 chlorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3 ethoxyphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3 fluorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3 methoxyphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (3,5 dimethylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 bromophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 chlorophenylthio)anthra[1,2-c][1,2,5]thiadiazole-6,11- dione; 4 (4 ethylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 fluorophenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 isopropylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 methoxyphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (4 tert butylphenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (benzylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (isopropylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (o tolylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 (phenylthio)anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; 4 [4 (methylthio)phenylthio]anthra[1,2 c][1,2,5]thiadiazole 6,11 dione; antineoplastic agent; sulfur substituted anthra[1,2 c ][1,2,5]thiadiazole 6,11 dione derivative; unclassified drug; unindexed drug; 4-(isopropylthio)anthra(1,2-c)(1,2,5)thiadiazole-6,11-dione; anthraquinone derivative; antineoplastic agent; sulfur; thiadiazole derivative; antineoplastic activity; apoptosis; Article; assay; cancer cell; cell proliferation; controlled study; cytotoxicity; drug synthesis; human; human cell; national health organization; chemical structure; chemistry; drug effects; drug screening; structure activity relation; synthesis; tumor cell line; Anthraquinones; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Structure-Activity Relationship; Sulfur; Thiadiazoles
Type
journal article