Synthesis And Anti-cancer Activities Of3-Oxo-3-Phenyl-2-(Phenyl-hydrazono)-Propionitrile Derivatives

The signal transducer and activator of transcription3(STAT3) is an important signal transductionprotein. Since it is closely related with cancer occurrence and development, inhibiting STAT3over-expression was reported to be able to fight against tumors. Recent research progress on STAT3smallmolecule inhibitors revealed a series of novel O-alkylamino-tethered derivatives of niclosamide, N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, celecoxib, as well as purine compounds.These compounds were discovered by screening techniques, Multiple Ligand Simultaneous Docking(MLSD), Quantitative Structure-Activity Relationships (QSAR).In the process of finding and screening of target compounds, XinliangMao found a new class ofsmall molecule compounds from tens of thousands of compounds. These compounds can inhibittheproliferation of a variety of acute and chronic tumor cells, including leukemia, multiple myeloma,lung cancer, prostate cancer, cervical cancer, Which screened out mayhave a better effect on the activityof STAT3target compounds3-Oxo-3-phenyl-2-(phenyl-hydrazono)-propionitrileand3-Oxo-3-(4-Chloro phenyl-2-(phenyl-hydrazono)-propionitrile.After retention parent core3-Oxo-3-phenyl-2-(phenyl-hydrazono)-propionitrile, by varying thesubstituents of the compounds designed and synthesized E1-E31, wherein E1-E26compound has notbeen reported.Thirty one3-Oxo-3-phenyl-2-(phenyl-hydrazono)-propionitrile derivatives were synthesized byfour steps using substituted benzoic acids, acetonitrile, substituted anilines. The structures werecharacterized by1H NMR, MS, and13C NMR. The anti-cancer activities of E1-E31against Hep G2,Du145, MBA-MD-231and NIH3T3(curcumin and stattic as controls) in vitro by MTT method wereinvestigated. The results showed that E5exhibited the strongest anti-cancer activities in vitro against three cancer cell.