Synthesis and molecular docking study of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as potential antitumor agents.
A series of novel coumarin derivatives containing 4,5-dihydropyrazole moiety as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 3d exhibited potentially high activity against human gastric cancer cell SGC-7901 with IC(50) value of 2.69 ± 0.60 μg/mL. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compounds 3d and 3f can strongly inhibit telomerase with IC(50) values of 2.0 ± 0.07 and 1.8 ± 0.35 μM, respectively. Docking simulation was performed to position compound 3d into the telomerase (3DU6) active site to determine the probable binding model.
Liu
Xin-Hua
XH
School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan 243002, PR China.
Liu
Hui-Feng
HF
Chen
Jin
J
Yang
Yang
Y
Song
Bao-An
BA
Bai
Lin-Shan
LS
Liu
Jing-Xin
JX
Zhu
Hai-Liang
HL
Qi
Xing-Bao
XB
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000970:Antineoplastic Agents; D003374:Coumarins; D011720:Pyrazoles; C031280:pyrazole; C030123:coumarin; D019098:Telomerase