4-Carbonyl-2,6-dibenzylidenecyclohexanone derivatives as small molecule inhibitors of STAT3 signaling pathway.
Inhibition of STAT3 signaling pathway is proposed to be a promising strategy for cancer treatment. In this study, a series of 4-carbonyl-2,6-dibenzylidenecyclohexanone derivatives were prepared and evaluated as anticancer agents. The most potent compound 13r was discovered to exhibit antiproliferative activity against a broad rang of cancer cell lines and relatively low cytotoxicity against normal human cells. Besides, 13r effectively suppressed STAT3 expression as well as phosphorylation, and surface plasmon resonance analysis confirmed the direct interaction of 13r with STAT3. Docking simulation showed that 13r could inhibit STAT3 by targeting SH2 domain. This study provided evidence for these compounds to be further developed as antitumor agents through inhibition of the STAT3 pathway.
Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Peng
P
Ji
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
Congmin
C
Yuan
Department of Chemistry, Jess and Mildred Fisher College of Science and Mathematics, Towson University, 8000 York Road, Towson, MD 21252, United States.
Shuhua
S
Ma
Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Junchao
J
Fan
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
Wei
W
Fu
Department of Medicinal Chemistry, College of Pharmaceutical Science, Soochow University, 199 Ren Ai Road, Suzhou 215123, PR China.
Chunhua
C
Qiao
D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D018909:src Homology Domains
D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D003512:Cyclohexanones; C000622784:N-(2-(diethylamino)ethyl)-3,5-bis(4-fluorobenzylidene)-4-oxocyclohexanecarboxamide; D050796:STAT3 Transcription Factor; D011065:Poly(ADP-ribose) Polymerases
Antitumor; Apoptosis; Curcumin; Inhibitors; STAT3