The Research For Synthesis And Antineoplastic Activity Of Novel Compounds Fusing Nucleosides’ Basic Groups And Oxoindole

It is reported that nucleosides’basic groups and oxoindole possess a wide range of biological activities,as well as they are significantly important synthon.Based on their significant biological activities,a series of novel compounds fusing nucleosides’basic groups and oxoindole were synthesized in this article via the fused theory of active functional groups.Two main research works were done in this article.（1）Given 3-Alkenyl-oxindole represents a key skeleton found in a number of natural products and pharmaceuticals,we firstly synthesized a series of3-alkenyl-oxindoles containing pyrimidine ring via the classic Knoevenagel condensation,which gave us a hope finding good bioactive lead compounds.During the research,we understood the plausible mechanism of synthesizing the desired targets via screening different reaction conditions and synthesized 38 desired3-alkenyl-oxindoles under the optimal reaction conditions.All the structures were characterized by ¹H NMR,¹³C NMR and MS-ESI,and the X-ray crystallographic structure of the desired compounds was confirmed.After that,the cytotoxicity of the whole compounds on human Leukemic cell lines（K562）,human non-small cell lung cancer cells（A549）and human prostate cancer cell lines（PC-3）were determined by MTT assay,with the cisplatin being the positive control drug.The results showed that the cytotoxicity of compounds YC-1-02、YC-1-11、YC-1-16、YC-1-17、YC-1-18、YC-1-25、YC-1-28 and YC-1-37 on human Leukemia cell line（K562）and human prostate cancer cell line（PC-3）were close to the cisplatin.（2）To get novel compounds possessing better antineoplastic activity and more targets,some new compounds based on the 3-alkenyl-oxindoles were to be synthezied.We found 3-pyrrolidinyl spirooxindoles possessed better antineoplastic activity and advantages of[3+2]cyclization reaction,after we consulted some articles about it,including easy operation and wide feasibility.We had an idea,convert3-alkenyl-oxindoles into 3-pyrrolidinyl spirooxindoles containing pyrimidine ring via a domino[3+2]cyclization reaction.To examine our hypothesis,we put the[3+2]cyclization reaction into istain,5-methyl-1-phenylhexa-1,4-dien-3-one and commercially available sarcosine.We were pleased to find the plausible mechanism of synthesizing the desired targets and synthesize 33 structurally diverse 3,2′-pyrrolidinyl spirooxindoles via the[3+2]cyclization reaction.All the structures were characterized by ¹H NMR,¹³C NMR and MS-ESI,and the X-ray crystallographic structures of some desired compounds were confirmed.At the same time,their cytotoxicity on human Leukemic cell lines（K562）,human non-small cell lung cancer cells（A549）and human prostate cancer cell lines（PC-3）were determined by MTT assay,with the cisplatin being the positive control drug.The results showed that the cytotoxicity of compounds YC-2-02,YC-2-05,YC-2-08,YC-2-10,YC-2-12,YC-2-13,YC-2-17,YC-2-18,YC-2-21,YC-2-25,YC-2-27,YC-2-28 and YC-2-30on human Leukemia cell line（K562）and human prostate cancer cell line（PC-3）were better than the cisplatin,which were much better than 3-alkenyl-oxindoles’.After the plausible mechanism and key information of the[3+2]cyclization reaction were verified,the cyclization reaction was put in use between the3-alkenyl-oxindoles,paraformaldehyde and sarcosine.We were pleased to find the[3+2]cyclization reaction worked well and 25 structurally diverse 3,3′-pyrrolidinyl spirooxindoles containing pyrimidine were synthesized in good to excellent yields.Their structures were characterized by ¹H NMR,¹³C NMR and MS-ESI,and the X-ray crystallographic structures of some desired compounds were confirmed.The cytotoxicity of the whole compounds on K562,A549 and PC-3 were determined by MTT assay,with the cisplatin being the positive control drug.The results showed that the cytotoxicity of 3,3′-pyrrolidinyl spirooxindoles on K562 is better.And,the cytotoxicity of compounds YC-3-07,YC-3-11,YC-3-12,YC-3-16,YC-3-22 and YC-3-23 on K562 were close to the cisplatin.