Synthesis, antiproliferative activities and telomerase inhibition evaluation of novel asymmetrical 1,2-disubstituted amidoanthraquinone derivatives
Journal
European Journal of Medicinal Chemistry
Journal Volume
47
Journal Issue
1
Pages
323-336
Date Issued
2012
Author(s)
Abstract
A series of diversely asymmetrical mono- or disubstituted 1,2-diamidoanthraquinone derivatives were synthesized and evaluated for drug-induced cytotoxicity by SRB assay, telomerase inhibitory activity by TRAP assay, and hTERT expression by SEAP assay. Interestingly, compounds 4, 11, 21, 32 and 36 exhibited selective potent antiproliferative activities by NCI with IC 50 values in the micromolar range. Of these, only compound 8 showed an IC 50 value of 0.95 μM against PC-3 cell lines (human prostate cancer) by SRB assay. All the synthesized compounds exhibited a poor or modest telomerase inhibitory activity by TRAP assay suggesting another mode of action for these compounds. Compound 11 showed broad inhibition against different types of cancer cell lines in the micromolar and submicromolar range. ? 2011 Elsevier Masson SAS. All rights reserved.
SDGs
Other Subjects
1 (2 chlorobenzamido) 2 (chloroacetamido) anthraquinone; 1 (2 fluorobenzamido) 2 (chloroacetamido) anthraquinone; 1 (2 methylbenzamido) 2 (chloroacetamido) anthraquinone; 1 (3 fluorobenzamido) 2 (chloroacetamido) anthraquinone; 1 (3 methylbenzamido) 2 (chloroacetamido) anthraquinone; 1 (4 chlorobenzamido) 2 (chloroacetamido) anthraquinone; 1 (4 fluorobenzamido) 2 (chloroacetamido) anthraquinone; 1 (amino) 2 (chloroacetamido) anthraquinone; 1 (benzamido) 2 (chloroacetamido) anthraquinone; 1 [(2 furoyl)amido] 2 (chloroacetamido) anthraquinone; 1 [(2,5 dimethyl 3 furoyl)amido] 2 (chloroacetamido) anthraquinone; 1 [(3 chloropropanyl)amido] 2 (chloroacetamido) anthraquinone; 1 [(4 chlorobutanyl)amido] 2 (chloroacetamido) anthraquinone; 1 [(5 isoxazolecarbonyl)amido] 2 (chloroacetamido) anthraquinone; 1 [2 (4 fluorophenyl)acetylamido] 2 (chloroacetamido) anthraquinone; 1 [2 (phenoxy)acetylamido] 2 (chloroacetamido) anthraquinone; 1 [2 (phenyl)acetylamido] 2 (chloroacetamido) anthraquinone; 1 [2 (phenylsulfanyl)acetylamido] 2 (chloroacetamido) anthraquinone; 1 [2 (trifluoromethyl)benzamido] 2 (chloroacetamido) anthraquinone; 1 [3 (trifluoromethyl)benzamido] 2 (chloroacetamido) anthraquinone; 1 [4 (trifluoromethyl)benzamido] 2 (chloroacetamido) anthraquinone; 1, 2 bis (chloroacetamido) anthraquinone; 1,2 bis (3 chloropropionamido) anthraquinone; 1,2 bis (4 chlorobutyramido) anthraquinone; 1,2 bis (4 methylbenzamido) anthraquinone; anthraquinone derivative; telomerase; telomerase reverse transcriptase; unclassified drug; unindexed drug; antineoplastic activity; article; cancer cell culture; controlled study; drug determination; drug inhibition; drug mechanism; drug potency; drug structure; drug synthesis; human; human cell; human cell culture; IC 50; prostate cancer; Anthraquinones; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Telomerase
Type
journal article