Synthesis and biological evaluation of novel N-methyl-picolinamide-4-thiol derivatives as potential antitumor agents.
A novel series of N-methylpicolinamide-4-thiol derivatives were synthesized and evaluated on human cancer cell lines. Among them, compound 6p displayed potent and broad-spectrum anti-proliferative activities in vitro on some human cancer cell lines, even better than sorafenib. The advanced kinase inhibitory assays showed that compound 6p could selectively inhibit Aurora-B kinase. The biological results were rationalized by the molecular docking study, which indicated the stable interactions of 6p with the Aurora-B kinase.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Ting-Ting
TT
Huang
Yun-Chuang
YC
Huang
Xiao-Yu
XY
Qing
Yong
Y
Xia
Xun
X
Luo
Ting-Hong
TH
Ye
Luo-Ting
LT
Yu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D064107:Aurora Kinase B; D064127:Aurora Kinases; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D010848:Picolinic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D011485:Protein Binding; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; C575301:N-methyl-picolinamide-4-thiol; D010848:Picolinic Acids; D047428:Protein Kinase Inhibitors; D013438:Sulfhydryl Compounds; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases