Structure-based design, synthesis and biological evaluation of novel anthra[1,2-d]imidazole-6,11-dione homologues as potential antitumor agents.
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.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Tsung-Chih
TC
Chen
Dah-Shyong
DS
Yu
Kuo-Feng
KF
Huang
Yung-Chien
YC
Fu
Chia-Chung
CC
Lee
Chun-Liang
CL
Chen
Fong-Chun
FC
Huang
Hsi-Hsien
HH
Hsieh
Jing-Jer
JJ
Lin
Hsu-Shan
HS
Huang
D000880:Anthraquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000880:Anthraquinones; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; C509186:TERT protein, human; D019098:Telomerase
Anthra[1,2-d]imidazole-6,11-dione; Cytostatic and cytotoxic activities; NCI 60-cell panel assay; Selectivity ratio