Synthesis And Antitumor Activities Of 3-alkenyl-bisoxindoles

In this article,we developed an efficient synthetic method for the construction of a new bisindole molecule which bonding two active motifs including 3-alkenyloxindole ring-fused 3,3′-disubstituted oxindole.We also screen their antitumor activitys.Firstly,synthesis of 5 isatins with differeent substitution groups through the Sandmeyer isonitroso acetyl aniline Isatin synthesis methed as the initial substrate.Secondly,synthesis of 12 3-substituted-isatins and 8 3-aryl(or alky)-N-Boc oxindoles according to the reported methed.Ultimately,synthesis of 3-alkenylbisoxindole via direct gamma-substitution of Morita–Baylis–Hillman carbonates of isatins with 3-substituted oxindoles with highly regioselective.We also chose an optimization of the reaction,catalyst,solvent,reaction time and alkaline conditions were screened,reached high yield 83%.Most of the Morita–Baylis–Hillman carbonate as substrates afford α-substitution products using the transition-metal palladium,organocatalysis,or Lewis base as catalyst reported in the literature.The reaction was carried out under mild reaction condition with high stereo selectivity.We totally synthesised 24 3-alkenyl-bisoxindolecompounds by this way.In addition,synthesis of 1 3-alkenyl-oxindole containing an active hydroge atom.In addition,these synthesized compounds were evaluated in vitro against PC-3(human prostate cancer cells)and K562(human leukemia cells)and A549(human pulmonary carcinoma)by an MTT-based assay,using the commercially available standard drug cisplatin as a control.The results demonstrated that compounds 3ba,3aa,and 3ca exhibited the best in vitro inhibitorys again PC-3(sthuman prostatecancer cells),and had almost comparable to the positive drug Cisplatin,and 3ba had a good inhibition ability on K562(human leukemia cells).The results indicated that 3-alkenyl-oxindolering-fused 3,3′-disubstituted oxindole may be useful for further biological screening as a antitumor lead compound.The research includes organic methodology,pharmaceutical chemistry,and pharmacology.Anti tumor activity in vitro screening reveals that bonding active motifi the afford 3-alkenyl-bisoxindoles have activity and can be used as a lead compound for antitumor.