唑类化合物和铂配合物的合成及其抗肿瘤活性研究
摘要
唑类化合物是一类重要的五元杂环化合物，许多衍生物已应用于工业，且在医学上表现出很好的抗癌、消炎、止痛、杀菌等性能。因此，近年来，唑类化合物得到人们的广泛关注，本文用常规方法和无溶剂研磨法合成了一系列唑衍生物，并以部分唑类化合物为配体，合成了铂配合物，并对部分配合物进行了体外抗癌活性测试，主要工作如下：
在无溶剂条件下，以苯甲酰肼和取代苯甲醛为起始原料，三氯异氰尿酸(TCCA)为环合剂，室温研磨反应10 min,制得2,5-二取代-1,3,4-噁二唑，收率75-88% (此反应若在常规加热条件下进行，需7-8 h,收率63-85%)，并利用元素分析、IR、~1H NMR对其结构进行了表征。实验结果表明，采用研磨法，可以大大缩短反应时间、提高收率，且对环境污染小。
以苯甲酰肼和取代苯甲醛为起始原料合成酰腙，再将酰腙在乙酸酐中环合，生成3-N-乙酰基-2,5-二取代-1,3,4-噁二唑，收率53-67%，得到6个新化合物，并利用元素分析、IR、~1H NMR对其结构进行了表征。
以水合肼和二硫化碳为起始原料，合成二氨基硫脲，将二氨基硫脲与取代苯甲醛在乙酸中加热，得到甲基-4-氨基-1,2,4-三唑-3-硫酮席夫碱，收率78-86%，得到6个新化合物，并利用元素分析、IR、~1H NMR对其结构进行了表征。
以上述所合成的唑类化合物为配体，合成相应的铂配合物，利用元素分析、IR、~1HNMR和UV对其结构进行了表征，并选取部分配合物进行了体外人肺腺癌细胞(A549)和人宫颈癌细胞(Hela)的抗癌活性测试。测试数据显示2,5-二苯基-1,3,4-噁二唑铂配合物和2-苯基-5-(4-甲氧基-苯基)-1,3,4-噁二唑铂配合物对人体肺腺癌细胞(A549)有一定的活性，IC_(50)值分别为20.06±1.56和58.72±2.24。
Azoles is an important class of heterocyclic compounds. Many derivates of them haveapplication in indusry. And in medicine, they show well biological activities in antiviral,antimicrobial, antineoplastic, fungicidal and inhibition of tyrosinase. Therefore, recent years,people pay more attention on the research of azoles. In this article, we synthesized someazoles by conventional methods, besides that, some derivates of azoles have been synthesizedunder solvent-free and catalyst-free conditions. Then, we synthesized platinum complexeswhich using azoles as ligands. We present some results as follows:
A series of 2-phenyl-5-aryl-1,3,4-oxadiazole were synthesized by grinding reaction ofbenzoyhydrazide, benzaldehyde and TCCA under solvent-free condition. The reactions werecompleted within 10 min giving the products in 75%~85% yields.The method has theadvantages of simple, rapid and environment friendly. Then synthesized platinum complexes.
We used benzaldehyde, benzoyhydrazide and acetic anhydride as starting reagents, synthesized3-acetyl-2-phenyl-5-aryl-1,3,4-oxadiazole by two steps. Then, synthesized platinumcomplexes.
We used hydrazine hydrate, carbon bisulfide, acetic acid and aldehyde as starting reagents,synthesized 5-methyl-4-amino-1,2,4-triazole-3-thione Schiff bases. Then synthesized platinumcomplexes.
The complexes were characterized and evaluated for their anti-tumor activity against somecancer cells in vitro by MTT method. Among them, complexes 13 and 15 show a certainanti-tumor activity.
在无溶剂条件下，以苯甲酰肼和取代苯甲醛为起始原料，三氯异氰尿酸(TCCA)为环合剂，室温研磨反应10 min,制得2,5-二取代-1,3,4-噁二唑，收率75-88% (此反应若在常规加热条件下进行，需7-8 h,收率63-85%)，并利用元素分析、IR、~1H NMR对其结构进行了表征。实验结果表明，采用研磨法，可以大大缩短反应时间、提高收率，且对环境污染小。
以苯甲酰肼和取代苯甲醛为起始原料合成酰腙，再将酰腙在乙酸酐中环合，生成3-N-乙酰基-2,5-二取代-1,3,4-噁二唑，收率53-67%，得到6个新化合物，并利用元素分析、IR、~1H NMR对其结构进行了表征。
以水合肼和二硫化碳为起始原料，合成二氨基硫脲，将二氨基硫脲与取代苯甲醛在乙酸中加热，得到甲基-4-氨基-1,2,4-三唑-3-硫酮席夫碱，收率78-86%，得到6个新化合物，并利用元素分析、IR、~1H NMR对其结构进行了表征。
以上述所合成的唑类化合物为配体，合成相应的铂配合物，利用元素分析、IR、~1HNMR和UV对其结构进行了表征，并选取部分配合物进行了体外人肺腺癌细胞(A549)和人宫颈癌细胞(Hela)的抗癌活性测试。测试数据显示2,5-二苯基-1,3,4-噁二唑铂配合物和2-苯基-5-(4-甲氧基-苯基)-1,3,4-噁二唑铂配合物对人体肺腺癌细胞(A549)有一定的活性，IC_(50)值分别为20.06±1.56和58.72±2.24。
Azoles is an important class of heterocyclic compounds. Many derivates of them haveapplication in indusry. And in medicine, they show well biological activities in antiviral,antimicrobial, antineoplastic, fungicidal and inhibition of tyrosinase. Therefore, recent years,people pay more attention on the research of azoles. In this article, we synthesized someazoles by conventional methods, besides that, some derivates of azoles have been synthesizedunder solvent-free and catalyst-free conditions. Then, we synthesized platinum complexeswhich using azoles as ligands. We present some results as follows:
A series of 2-phenyl-5-aryl-1,3,4-oxadiazole were synthesized by grinding reaction ofbenzoyhydrazide, benzaldehyde and TCCA under solvent-free condition. The reactions werecompleted within 10 min giving the products in 75%~85% yields.The method has theadvantages of simple, rapid and environment friendly. Then synthesized platinum complexes.
We used benzaldehyde, benzoyhydrazide and acetic anhydride as starting reagents, synthesized3-acetyl-2-phenyl-5-aryl-1,3,4-oxadiazole by two steps. Then, synthesized platinumcomplexes.
We used hydrazine hydrate, carbon bisulfide, acetic acid and aldehyde as starting reagents,synthesized 5-methyl-4-amino-1,2,4-triazole-3-thione Schiff bases. Then synthesized platinumcomplexes.
The complexes were characterized and evaluated for their anti-tumor activity against somecancer cells in vitro by MTT method. Among them, complexes 13 and 15 show a certainanti-tumor activity.
引文
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