席夫碱类化合物的合成及其抗肿瘤活性的研究
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摘要
研究发现,席夫碱类化合物在医药、有机合成、分析化学以及催化等方面有着广泛的应用。其中,一些缩氨硫脲类化合物具有明显的抗肿瘤活性。
本文合成了肼基二硫代甲酸苄酯席夫碱,肼基二硫代甲酸甲酯席夫碱,缩氨硫脲,苯甲酰腙等一系列席夫碱类化合物。通过正交试验优化了肼基二硫代甲酸苄酯的反应条件,得到最佳收率为77%;探讨了不同因素对肼基二硫代甲酸苄酯席夫碱合成的影响。通过红外光谱、质谱和核磁共振谱确证了部分化合物的结构;培养得到3个化合物J20,Z14和Z16的单晶,并用X射线单晶衍射仪测定了它们的晶体结构。
对部分化合物进行了体外抗肿瘤活性测试。将化合物J27、J35、J700和J705对MOLT-4人白血病进行了抗肿瘤生物活性体外筛选实验,初步结果表明:从10~(-8)mol.L~(-1)到10~(-5)mol.L~(-1)的浓度范围内,四个化合物对MOLT-4人白血病癌细胞的抑制率都达到了100%,具有明显的抗肿瘤活性。对化合物J25和J600进行了体外肿瘤细胞增殖抑制试验,结果表明:J600对人肝癌SMMC7721细胞和人结直肠癌COLO205细胞具有强体外增殖抑制作用,其IC_(50)均小于1μmol/L;J25对上述两种肿瘤细胞也具有较强体外增殖抑制作用,其IC_(50)均小于10μmol/L。
According to the studies,it was found that Schiff bases have a variety of use in medicine,organic synthesis,analysis chemistry and catalysis,and so on.Some thiosemicarbazones possess definite antitumor activity.
A series of derivatives of Schiff bases such as sulphur-containing Schiff bases and thiosemicarbazones were synthesized.Benzyl-dithiocarbazate's optimum parameters were established by orthogonal tests,whose optimal yield was 77%.Many conditions have been discussed about the reaction.The structures of some derivatives have been characterized by means of IR,MS and HNMR.Three crystal structures of derivatives were determined by single crystal X-ray diffraction analysis. Antitumor activity of sulphur-containing Schiff bases and thiosemicarbazones has also been investigated in vitro.The antitumor activity against man Leukemia MOLT-4 for four compounds J27,J35,J700 and J705 has been tested.The results show that all of them have excellent antitumor activity against man Leukemia MOLT-4,which keep 100 percent during the density change from 10~(-8)mol.L(-1)to 10(-5)mol.L(-1).Besides,the results show that two compounds J600 and J25 have excellent inhibition effects on SMMC7721 and COLO205 cell growth.The IC_(50)(72 h)of J600 on SMMC7721 and COLO205 cells is no more than 1μmol/L,and that of J25 is no more than 10μmol/L.
本文合成了肼基二硫代甲酸苄酯席夫碱,肼基二硫代甲酸甲酯席夫碱,缩氨硫脲,苯甲酰腙等一系列席夫碱类化合物。通过正交试验优化了肼基二硫代甲酸苄酯的反应条件,得到最佳收率为77%;探讨了不同因素对肼基二硫代甲酸苄酯席夫碱合成的影响。通过红外光谱、质谱和核磁共振谱确证了部分化合物的结构;培养得到3个化合物J20,Z14和Z16的单晶,并用X射线单晶衍射仪测定了它们的晶体结构。
对部分化合物进行了体外抗肿瘤活性测试。将化合物J27、J35、J700和J705对MOLT-4人白血病进行了抗肿瘤生物活性体外筛选实验,初步结果表明:从10~(-8)mol.L~(-1)到10~(-5)mol.L~(-1)的浓度范围内,四个化合物对MOLT-4人白血病癌细胞的抑制率都达到了100%,具有明显的抗肿瘤活性。对化合物J25和J600进行了体外肿瘤细胞增殖抑制试验,结果表明:J600对人肝癌SMMC7721细胞和人结直肠癌COLO205细胞具有强体外增殖抑制作用,其IC_(50)均小于1μmol/L;J25对上述两种肿瘤细胞也具有较强体外增殖抑制作用,其IC_(50)均小于10μmol/L。
According to the studies,it was found that Schiff bases have a variety of use in medicine,organic synthesis,analysis chemistry and catalysis,and so on.Some thiosemicarbazones possess definite antitumor activity.
A series of derivatives of Schiff bases such as sulphur-containing Schiff bases and thiosemicarbazones were synthesized.Benzyl-dithiocarbazate's optimum parameters were established by orthogonal tests,whose optimal yield was 77%.Many conditions have been discussed about the reaction.The structures of some derivatives have been characterized by means of IR,MS and HNMR.Three crystal structures of derivatives were determined by single crystal X-ray diffraction analysis. Antitumor activity of sulphur-containing Schiff bases and thiosemicarbazones has also been investigated in vitro.The antitumor activity against man Leukemia MOLT-4 for four compounds J27,J35,J700 and J705 has been tested.The results show that all of them have excellent antitumor activity against man Leukemia MOLT-4,which keep 100 percent during the density change from 10~(-8)mol.L(-1)to 10(-5)mol.L(-1).Besides,the results show that two compounds J600 and J25 have excellent inhibition effects on SMMC7721 and COLO205 cell growth.The IC_(50)(72 h)of J600 on SMMC7721 and COLO205 cells is no more than 1μmol/L,and that of J25 is no more than 10μmol/L.
引文
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