Synthesis and molecular docking studies of novel 2-chloro-pyridine derivatives containing flavone moieties as potential antitumor agents.
A series of novel 2-chloro-pyridine derivatives containing flavone, chrome or dihydropyrazole moieties as potential telomerase inhibitors were synthesized. The bioassay tests showed that compounds 6e and 6f exhibited some effect against gastric cancer cell SGC-7901 with IC(50) values of 22.28+/-6.26 and 18.45+/-2.79 microg/mL, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results showed that compound 6e can strongly inhibit telomerase with IC(50) value of 0.8+/-0.07 microM. Docking simulation was performed to position compound 6e into the active site of telomerase (3DU6) to determine the probable binding model.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Xin-Hua
XH
Liu
Hui-Feng
HF
Liu
Xu
X
Shen
Bao-An
BA
Song
Pinaki S
PS
Bhadury
Hai-Liang
HL
Zhu
Jin-Xing
JX
Liu
Xing-Bao
XB
Qi
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D047309:Flavones / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D047309:Flavones; D011725:Pyridines; C083126:2-chloropyridine