Synthesis, biological evaluation, and molecular docking studies of 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety as potential antitumor agents.
A series of new 2-chloropyridine derivatives possessing 1,3,4-oxadiazole moiety were synthesized. Antiproliferative assay results indicated that compounds 6o and 6u exhibited the most potent activity against gastric cancer cell SGC-7901, which was more potent than the positive control. Especially, compound 6o exhibited significant telomerase inhibitory activity (IC(50)=2.3±0.07μM), which was comparable to the positive control ethidium bromide. Docking simulation was performed to position compound 6o into the active site of telomerase (3DU6) to determine the probable binding model.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Qing-Zhong
QZ
Zheng
Xiao-Min
XM
Zhang
Ying
Y
Xu
Kui
K
Cheng
Qing-Cai
QC
Jiao
Hai-Liang
HL
Zhu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008968:Molecular Conformation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D017434:Protein Structure, Tertiary; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism
C556001:2-chloro-5-(((5-(2-hydroxy-4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)thio)methyl)pyridine; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011725:Pyridines; C083126:2-chloropyridine; D019098:Telomerase