杂环含硫Schiff碱及其过渡金属配合物的合成、表征和生物活性研究
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摘要
杂环缩氨基硫脲具有良好的生物活性。近年来,杂环含硫Schiff碱及其金属
配合物因其良好的抑菌、抗肿瘤活性引起了人们的广泛关注。以往的研究主要集
中在吡啶类、呋喃类含硫Schiff碱及其过渡金属配合物上。而吡嗪类、噻唑类含
硫Schiff碱及其过渡金属配合物则鲜有报道。本文的主要内容如下:
1. 2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其金属配合物的合成与表征。
合成了2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其双螫合锌(Ⅱ)、
锰(Ⅱ)和单螯合的铜(Ⅱ)的金属配合物,并通过元素分析、质谱、红外光谱、
电子光谱、核磁共振氢谱和摩尔电导等测试手段进行了表征,确定了其组成和可
能的结构。
2. 2-乙酰基噻唑缩肼基二硫代甲酸苄酯Schiff碱和2-乙酰基噻唑缩氨基硫脲schiff碱(?)
合成了2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱和2-乙酰基噻唑缩氨基
硫脲。并通过元素分析、质谱、红外光潜、核磁共振氢谱和核磁共振碳谱等测试
手段进行了表征,确定了其组成和可能的结构。
3. 2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其过渡金属配合物的抑菌活
性研究。
分别对2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其双螯合锌(Ⅱ)、锰
(Ⅱ)和单螯合的铜(Ⅱ)的金属配合物测试了抑菌活性,实验菌株为革兰氏阳
性菌(金黄色葡萄球菌、苏云金芽孢杆菌、巨大芽孢杆菌和枯草芽孢杆菌)和革
兰氏阴性菌(大肠杆菌、铜绿假单孢菌和恶臭假单孢菌)。抑菌活性测试表明:
(1) 配体和配合物对革兰氏阳性菌和革兰氏阴性菌均有一定的活性。(2) 配合
物的活性强于配体的。(3) 化合物的活性和化合物的浓度不呈简单的线性关系,
而是在一定浓度范围内有一个最大活性值。
4. 对已合成化合物的抗稻瘟霉活性筛选
为在已合成化合物中寻找抗肿瘤先导化合物,我们采用了稻瘟霉模型筛选法。
抗稻瘟霉活性实验表明:上述化合物有不同程度的活性,而2-乙酰基噻唑缩肼基
二硫代甲酸苄酯Schiff碱的活性最强。
The wide variety of biological activity was exhibited by heterocyclic thiosemicarbazaones .In the recent research, more attention was paid to the Schiff bases and their metal complexes for their significant antibacterial and antitumor activity. Previous studies have centred mainly on transition metal complexes of sulfur-containing Schiff bases with pyridine or furan series. However the complexes of sulfur-containing Schiff bases with pyrazine or thiazole series were seldom reported. Our main job was described as below;l.Synthesis and Characterization of New Transition Metal Complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine.New bis-chelated Zinc(II), Manganese(II) and mono- chelated Copper(II) complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine were prepared. The compounds were characterized by elementary analysis, Mass spectrum,IR Spectra, Electronic Spectra, 1H NMR Spectra and Molar conductance measurements.And their composition and probably structure are confirmed.2. Synthesis and Characterization of New Schiff base ligands derived from S-benzyldithiocarbazate, thiosemicarbazone and 2-acetylthiazole.Two kinds of Schiff bases derived from S-benzyldithiocarbazate, thiosemicarbazone and 2-acetylthiazole were prepared. The compounds were characterized by elementary analysis, IR Spectra, Mass spectrum, 1H NMR, 13C NMR Spectra and their composition and probably structure are confirmed.3. The antibacterial activity of New Transition Metal Complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine.The antibacterial activity of Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine and their bis-chelated Zinc(II) , Manganese(II) and mon- chelated Copper(II) complexes have been tested against gram-positive bacterium (Staphylococcus aureus, Bacillus thuringiensis, Bacillus megaterium
and Bacillus subitilis) and gram-negative bacterium(Escherichia coli, Pseudomomas aeruginosa and Pseudomomas putida). The antibacterial activity results are as follows:(1) the ligands and complexes are differently effective against gram-positive bacterium and gram-negative bacterium.(2) The antibacterial activity of the complexes is stronger than the ligands.(3) The antibacterial activity isn't stronger when the concentration of the compound becames larger,but have the best effect in a certain range. 4. Screening of anti-pyricularia oryzae activity of the complexes that had been prepared.To seek forerunner antitumor drugs from compounds that had been prepared, the screening model of pyricularia oryzae was applied.The anti- pyricularia oryzae activity results showed that the compounds are differently effective against pyricularia oryzae ,and that activity of Schiff bases derived from S-benzyldithiocarbazate and 2-acetylthiazolc are strongest.
配合物因其良好的抑菌、抗肿瘤活性引起了人们的广泛关注。以往的研究主要集
中在吡啶类、呋喃类含硫Schiff碱及其过渡金属配合物上。而吡嗪类、噻唑类含
硫Schiff碱及其过渡金属配合物则鲜有报道。本文的主要内容如下:
1. 2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其金属配合物的合成与表征。
合成了2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其双螫合锌(Ⅱ)、
锰(Ⅱ)和单螯合的铜(Ⅱ)的金属配合物,并通过元素分析、质谱、红外光谱、
电子光谱、核磁共振氢谱和摩尔电导等测试手段进行了表征,确定了其组成和可
能的结构。
2. 2-乙酰基噻唑缩肼基二硫代甲酸苄酯Schiff碱和2-乙酰基噻唑缩氨基硫脲schiff碱(?)
合成了2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱和2-乙酰基噻唑缩氨基
硫脲。并通过元素分析、质谱、红外光潜、核磁共振氢谱和核磁共振碳谱等测试
手段进行了表征,确定了其组成和可能的结构。
3. 2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其过渡金属配合物的抑菌活
性研究。
分别对2-乙酰基吡嗪缩肼基二硫代甲酸苄酯Schiff碱及其双螯合锌(Ⅱ)、锰
(Ⅱ)和单螯合的铜(Ⅱ)的金属配合物测试了抑菌活性,实验菌株为革兰氏阳
性菌(金黄色葡萄球菌、苏云金芽孢杆菌、巨大芽孢杆菌和枯草芽孢杆菌)和革
兰氏阴性菌(大肠杆菌、铜绿假单孢菌和恶臭假单孢菌)。抑菌活性测试表明:
(1) 配体和配合物对革兰氏阳性菌和革兰氏阴性菌均有一定的活性。(2) 配合
物的活性强于配体的。(3) 化合物的活性和化合物的浓度不呈简单的线性关系,
而是在一定浓度范围内有一个最大活性值。
4. 对已合成化合物的抗稻瘟霉活性筛选
为在已合成化合物中寻找抗肿瘤先导化合物,我们采用了稻瘟霉模型筛选法。
抗稻瘟霉活性实验表明:上述化合物有不同程度的活性,而2-乙酰基噻唑缩肼基
二硫代甲酸苄酯Schiff碱的活性最强。
The wide variety of biological activity was exhibited by heterocyclic thiosemicarbazaones .In the recent research, more attention was paid to the Schiff bases and their metal complexes for their significant antibacterial and antitumor activity. Previous studies have centred mainly on transition metal complexes of sulfur-containing Schiff bases with pyridine or furan series. However the complexes of sulfur-containing Schiff bases with pyrazine or thiazole series were seldom reported. Our main job was described as below;l.Synthesis and Characterization of New Transition Metal Complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine.New bis-chelated Zinc(II), Manganese(II) and mono- chelated Copper(II) complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine were prepared. The compounds were characterized by elementary analysis, Mass spectrum,IR Spectra, Electronic Spectra, 1H NMR Spectra and Molar conductance measurements.And their composition and probably structure are confirmed.2. Synthesis and Characterization of New Schiff base ligands derived from S-benzyldithiocarbazate, thiosemicarbazone and 2-acetylthiazole.Two kinds of Schiff bases derived from S-benzyldithiocarbazate, thiosemicarbazone and 2-acetylthiazole were prepared. The compounds were characterized by elementary analysis, IR Spectra, Mass spectrum, 1H NMR, 13C NMR Spectra and their composition and probably structure are confirmed.3. The antibacterial activity of New Transition Metal Complexes with Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine.The antibacterial activity of Schiff base ligands derived from S-benzyldithiocarbazate and 2-acetylpyrazine and their bis-chelated Zinc(II) , Manganese(II) and mon- chelated Copper(II) complexes have been tested against gram-positive bacterium (Staphylococcus aureus, Bacillus thuringiensis, Bacillus megaterium
and Bacillus subitilis) and gram-negative bacterium(Escherichia coli, Pseudomomas aeruginosa and Pseudomomas putida). The antibacterial activity results are as follows:(1) the ligands and complexes are differently effective against gram-positive bacterium and gram-negative bacterium.(2) The antibacterial activity of the complexes is stronger than the ligands.(3) The antibacterial activity isn't stronger when the concentration of the compound becames larger,but have the best effect in a certain range. 4. Screening of anti-pyricularia oryzae activity of the complexes that had been prepared.To seek forerunner antitumor drugs from compounds that had been prepared, the screening model of pyricularia oryzae was applied.The anti- pyricularia oryzae activity results showed that the compounds are differently effective against pyricularia oryzae ,and that activity of Schiff bases derived from S-benzyldithiocarbazate and 2-acetylthiazolc are strongest.
引文
[1] Schiff H,Annis Chem,1864,131:118
[2] 游效曾,孟庆金,韩万书.配位化学进展,北京:高等教育出版社,2001:17
[3] 王建华,雷文,王远亮等.重庆大学学报,2002. 25(7)
[4] 王建华,雷文,王远亮等.化学研究与应用,2003,15(3)
[5] 宋琳 谢毓元 王惠贞等.中国药物化学杂志,2000,10(2) :92
[6] 林明丽,崔秀兰,韩利民等.内蒙古工业大学学报,2003,22(1)
[7] 梁芳珍,徐克龙,任建成.合成化学,1999,7(2) :121
[8] 祝振富,黎植昌,张积霞等.西南师范大学学报(自然科学版),1997,22(1) :50
[9] Chohan Z H, Kausar S. Metal. Met-Based Drugs, 2000, 7(1) : 17
[10] Chohan Z H Sherazi S K A, Praveen M et al. Met-Based Drugs, 1998, 5(6) :347
[11] Srivastava V, Mishra A P. J.Indian Chem. Soc. 1995, 72(1) :47
[12] Bolos C A, Nikolov G S, Ekateriniadou L etal. Met.-Based. Drugs, 1998, 5(6) :323
[13] Rao NR, Rao P V, Reddy G V etal. Indian J. Chem., 1987, 26A(10) , 887
[14] Pardeya S N, Sriram D, Nath G. Clercq Erik de.Arzneim. Forsch, 2000, 50(1) :55
[15] Chohan Z H, Sherazi S K A and Praveen M, et al. Met.-Based Drugs, 1998, 5(6) : 347
[16] Sridhav S K, Pandeya S N, Bajpai S K etal. S Indian Drugs, 1999, 36(6) :412
[17] 徐琍,徐世平.药学学报,2000,35(4) :269
[18] 汪焱钢,曹蕾,杨军等.华中师范大学学报(自然科学版),1995,12(4) :486
[19] 曹蕾,杨军,刘国华等.华中师范大学学报(自然科学版),1997,31(4) :434 汪焱钢 曹蕾 杨军等。高等学校化学学报,1999,20(12) :1903
[20] 芦冰熙,李淑贤,叶文法等.湖南化工,2000,30(5) :42
[21] 芦冰熙,刘小鹏,王胜.华中师范大学学报(自然科学版),2000,34(4) :424
[22] 陆爱红,周青春,曹蕾等.华中师范大学学报(自然科学版),2000,34(4) :447
[23] 李彦锋,马应霞等.功能高分了学报 2001,2:221
[24] 章明,陈振锋,梁宏等.广西师范大学学报(自然科学版),2002,20(3) :42
[25] 杜鸣,梁芳珍,唐波,等.高等学校化学学报,1999,20(3) :369
[26] 祝心德,乐芝凤,吴自慎,等.无机化学学报,1994,10(2) :136
[27] 贤景春,哈日巴拉,曹高娃等.化学研究与应用,2000,12(4) :437
[28] 周毓萍,杨正银,于红娟等.稀土,1998,19(1)
[29] 方东,吉成荣.化学试剂,1997,19(6) :367
[30] 刘建宁,赵建设,任友贤等.化学研究与应用,1997,9(4)
[31] 赵全芹,王兴坡,柳翠英等.化学试剂,2001,23(4) :224
[32] 毕思玮,李桂芝,刘树祥等.无机化学学报,1998,14(2)
[33] 唐慧安,王流芳,赵恺寅等.稀土,2002,23(5)
[34] 唐慧安,王哲民,朱巧军等.兰州大学学报,2001,37(1)
[35] 朱巧军,戴荣斌,李勤喜筲.无机化学学报,2001,17(6)
[36] 杨昌晖,杨志斌.分析试验室.1994,13(4) :9
[37] 赵文献, 赵明根。化学试剂,1998,20(6) :366
[38] 赵文献, 赵明根。化学试剂,1999,21(1) :4
[39] 李锦州,沙靖全,安郁美等。中国稀土学报,2002,20(10)
[40] 王兴坡,赵全芹, 王德凤等.中国药科大学学报,1997,28(3) :180
[41] M.T.H. Tarafder, Khoo Teng Jin , Karen A. Crouse, et al. Polyhedron 2002 21 2547_ 2554
[42] 胡惟孝,孙楠,杨忠愚等.中国药物化学杂志,2001,11(3)
[43] 周守明,金昱泰.核化学与放射化学1999,21(4)
[44] 隗兰华,吴严,王法军等.武汉大学学报(理学版),2003,49(6)
[45] 薛照明,张宣军,田玉鹏等.无机化学学报,2002,18(10)
[46] 薛照明,田玉鹏,王东等.中国科学(B辑)2003,33(3) .
[2] 游效曾,孟庆金,韩万书.配位化学进展,北京:高等教育出版社,2001:17
[3] 王建华,雷文,王远亮等.重庆大学学报,2002. 25(7)
[4] 王建华,雷文,王远亮等.化学研究与应用,2003,15(3)
[5] 宋琳 谢毓元 王惠贞等.中国药物化学杂志,2000,10(2) :92
[6] 林明丽,崔秀兰,韩利民等.内蒙古工业大学学报,2003,22(1)
[7] 梁芳珍,徐克龙,任建成.合成化学,1999,7(2) :121
[8] 祝振富,黎植昌,张积霞等.西南师范大学学报(自然科学版),1997,22(1) :50
[9] Chohan Z H, Kausar S. Metal. Met-Based Drugs, 2000, 7(1) : 17
[10] Chohan Z H Sherazi S K A, Praveen M et al. Met-Based Drugs, 1998, 5(6) :347
[11] Srivastava V, Mishra A P. J.Indian Chem. Soc. 1995, 72(1) :47
[12] Bolos C A, Nikolov G S, Ekateriniadou L etal. Met.-Based. Drugs, 1998, 5(6) :323
[13] Rao NR, Rao P V, Reddy G V etal. Indian J. Chem., 1987, 26A(10) , 887
[14] Pardeya S N, Sriram D, Nath G. Clercq Erik de.Arzneim. Forsch, 2000, 50(1) :55
[15] Chohan Z H, Sherazi S K A and Praveen M, et al. Met.-Based Drugs, 1998, 5(6) : 347
[16] Sridhav S K, Pandeya S N, Bajpai S K etal. S Indian Drugs, 1999, 36(6) :412
[17] 徐琍,徐世平.药学学报,2000,35(4) :269
[18] 汪焱钢,曹蕾,杨军等.华中师范大学学报(自然科学版),1995,12(4) :486
[19] 曹蕾,杨军,刘国华等.华中师范大学学报(自然科学版),1997,31(4) :434 汪焱钢 曹蕾 杨军等。高等学校化学学报,1999,20(12) :1903
[20] 芦冰熙,李淑贤,叶文法等.湖南化工,2000,30(5) :42
[21] 芦冰熙,刘小鹏,王胜.华中师范大学学报(自然科学版),2000,34(4) :424
[22] 陆爱红,周青春,曹蕾等.华中师范大学学报(自然科学版),2000,34(4) :447
[23] 李彦锋,马应霞等.功能高分了学报 2001,2:221
[24] 章明,陈振锋,梁宏等.广西师范大学学报(自然科学版),2002,20(3) :42
[25] 杜鸣,梁芳珍,唐波,等.高等学校化学学报,1999,20(3) :369
[26] 祝心德,乐芝凤,吴自慎,等.无机化学学报,1994,10(2) :136
[27] 贤景春,哈日巴拉,曹高娃等.化学研究与应用,2000,12(4) :437
[28] 周毓萍,杨正银,于红娟等.稀土,1998,19(1)
[29] 方东,吉成荣.化学试剂,1997,19(6) :367
[30] 刘建宁,赵建设,任友贤等.化学研究与应用,1997,9(4)
[31] 赵全芹,王兴坡,柳翠英等.化学试剂,2001,23(4) :224
[32] 毕思玮,李桂芝,刘树祥等.无机化学学报,1998,14(2)
[33] 唐慧安,王流芳,赵恺寅等.稀土,2002,23(5)
[34] 唐慧安,王哲民,朱巧军等.兰州大学学报,2001,37(1)
[35] 朱巧军,戴荣斌,李勤喜筲.无机化学学报,2001,17(6)
[36] 杨昌晖,杨志斌.分析试验室.1994,13(4) :9
[37] 赵文献, 赵明根。化学试剂,1998,20(6) :366
[38] 赵文献, 赵明根。化学试剂,1999,21(1) :4
[39] 李锦州,沙靖全,安郁美等。中国稀土学报,2002,20(10)
[40] 王兴坡,赵全芹, 王德凤等.中国药科大学学报,1997,28(3) :180
[41] M.T.H. Tarafder, Khoo Teng Jin , Karen A. Crouse, et al. Polyhedron 2002 21 2547_ 2554
[42] 胡惟孝,孙楠,杨忠愚等.中国药物化学杂志,2001,11(3)
[43] 周守明,金昱泰.核化学与放射化学1999,21(4)
[44] 隗兰华,吴严,王法军等.武汉大学学报(理学版),2003,49(6)
[45] 薛照明,张宣军,田玉鹏等.无机化学学报,2002,18(10)
[46] 薛照明,田玉鹏,王东等.中国科学(B辑)2003,33(3) .