Synthesis and potent antileukemic activities of 10-benzyl-9(10H)-acridinones.
A novel series of 10-benzyl-9(10H)-acridinones and 1-benzyl-4-piperidones were synthesized and tested for their in vitro antitumor activities against CCRF-CEM cells. Assay-based antiproliferative activity study using CCRF-CEM cell lines revealed that the acridone group and the substitution pattern on the benzene unit had significant effect on cytotoxicity of this series of compounds, among which 10-(3,5-dimethoxy)benzyl-9(10H)-acridinone (3b) was found to be the most active compound with IC(50) at about 0.7 microM. Compound 3b was also found to have antiproliferative activity against two other human leukemic cell lines K562 and HL60 using the MTT assay. The antitumor effect of 3b is believed to be due to the induction of apoptosis, which is further confirmed by PI (Propidium iodide) staining and Annexin V-FITC/PI staining assay using flow cytometry analysis.
Gao
Chunmei
C
The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University, Lishui Road, Shenzhen 518055, PR China.
Jiang
Yuyang
Y
Tan
Chunyan
C
Zu
Xuyu
X
Liu
Huachen
H
Cao
Derong
D
D054831:Acridones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D010881:Piperidones / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D054831:Acridones; D000970:Antineoplastic Agents; D010881:Piperidones; D016650:Fluorescein-5-isothiocyanate; D001554:Benzene