Bis(2-acetylpyrazine) thiocarbonohydrazone and preparation method and application of bismuth (III) complex thereof

Abstract

The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of bis(2-acetylpyrazinyl) thiobisemicarbazone and its bismuth (III) complex and its application in the preparation of anticancer drugs. The molecular formula of the complex is [Bi(HL)(NO3)2(H2O)], wherein H2L represents bis(2-acetylpyrazine) thiobisemicarbazone, namely bis(2-acetylpyrazine)thiocarbonohydrazone. Its molecular structure is composed of a six-dentate coordinated bismuth ion, two monodentate nitrate ions, a coordinated water molecule and a single deprotonated N2S tridentate ligand (2-acetylpyrazinyl) Composition of thiobisemicarbazone. The complex has obvious inhibitory effect on the growth of human colorectal cancer cell HCT-116 and human liver cancer cell HepG2, and the research results provided by the invention provide an experimental basis for the application of the bismuth metal complex in medicine.

Description

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to a preparation method of bis(2-acetylpyrazinyl) thiobisemicarbazone and its bismuth (III) complex and the application in anticancer drugs. Background technique

[0002] Since Hamre et al first discovered that thiosemicarbazones have antiviral activity in 1950 (see C. S. Jr, S. H. Smith, J. Cdrach, D. L. Klayman, Antimicrobial Agents and Chemotherapy, 1981, 19: 682-685), successively found that thiosemicarbazone compounds not only have antiviral activity, but also have various biological activities such as antibacterial, antitumor, antileprosy, antituberculosis and antimalarial (see N. Fujii, J. P. Mallari, E. J. Hansell, Z. Mackey, P. Doyle, Y. M. Zhou, J. Gut, Bioorg. Med. Chem. Lett . 2005, 15: 121-125; J. Easmon, G. Pürstinger, G. Heinisch, T. Roth, H. H. Fiebig, W. Holzer, W. Jöger, M. Jenny, J. Hofmann, J. Med. Chem. 2001, 44: 2164-2171).

[0003] ...

Examples

Embodiment 1

[0038] The preparation method of two (2-acetylpyrazinyl) thiobisemicarbazones, it comprises the steps:

[0039] 1) Synthesize the required 1.3-symmetric dithiosemicarbazide according to the literature method (see Sheng Mei, Jiang Yanqing, Lu Zhengwei, Journal of Jiangsu Institute of Technology , 2004 , 16(1) : 35-39);

[0040] 2) Add 1.3-symmetric dithiosemicarbazide (1.00 g, 10 mmol) and 2-acetylpyrazine (2.40 g, 20 mmol) into a flask containing 50 mL of ethanol at room temperature, and then add 0.35 mL of glacial acetic acid dropwise , Mixed and then stirred and refluxed for 4h, cooled, filtered, and the precipitate was recrystallized with ethanol and dried in vacuum to obtain an orange-red powder with a yield of about 75%. Elemental analysis results measured value: C 49.87, H 4.18, N 35.78; calculated value C 13 h 13 N 8 S (%): C 49.97, H 4.09, N 35.90; IR (KBr, cm -1 ): ν (C=N) 1614 cm -1 , ν (C=S) 852 cm -1 , ν (N=N) 1104 cm -1 .

[0041] The preparation...

Embodiment 2

[0044] The preparation method of two (2-acetylpyrazinyl) thiobisemicarbazones, it comprises the steps:

[0045] 1) Synthesize the required 1.3-symmetric dithiosemicarbazide according to the literature method (see Sheng Mei, Jiang Yanqing, Lu Zhengwei, Journal of Jiangsu Institute of Technology , 2004 , 16(1) : 35-39);

[0046] 2) Add 1.3-symmetric dithiosemicarbazide (1.00 g, 10 mmol) and 2-acetylpyrazine (3.00 g, 25 mmol) into a flask containing 50 mL of methanol at room temperature, and then add 0.35 mL of glacial acetic acid dropwise , Mixed and then stirred and refluxed for 4h, cooled, filtered, and the precipitate was recrystallized with methanol and then vacuum-dried to obtain an orange-red powder with a yield of about 81%. Elemental analysis results measured value: C 49.87, H 4.18, N 35.78; calculated value C 13 h 13 N 8 S (%): C 49.97, H 4.09, N 35.90; IR (KBr, cm -1 ): ν (C=N) 1614 cm -1 , ν (C=S) 852 cm -1 , ν (N=N) 1104 cm -1 .

[0047] The prepara...

technical field

[0001] The invention belongs to the technical field of medicinal chemistry, and specifically relates to a preparation method of bis(2-acetylpyrazinyl) thiobisemicarbazone and its bismuth (III) complex and the application in anticancer drugs. Background technique

[0002] Since Hamre et al first discovered that thiosemicarbazones have antiviral activity in 1950 (see C. S. Jr, S. H. Smith, J. Cdrach, D. L. Klayman, Antimicrobial Agents and Chemotherapy, 1981, 19: 682-685), successively found that thiosemicarbazone compounds not only have antiviral activity, but also have various biological activities such as antibacterial, antitumor, antileprosy, antituberculosis and antimalarial (see N. Fujii, J. P. Mallari, E. J. Hansell, Z. Mackey, P. Doyle, Y. M. Zhou, J. Gut, Bioorg. Med. Chem. Lett . 2005, 15: 121-125; J. Easmon, G. Pürstinger, G. Heinisch, T. Roth, H. H. Fiebig, W. Holzer, W. Jöger, M. Jenny, J. Hofmann, J. Med. Chem. 2001, 44: 2164-2171).

[0003] ...

Examples

Embodiment 1

[0038] The preparation method of two (2-acetylpyrazinyl) thiobisemicarbazones, it comprises the steps:

[0039] 1) Synthesize the required 1.3-symmetric dithiosemicarbazide according to the literature method (see Sheng Mei, Jiang Yanqing, Lu Zhengwei, Journal of Jiangsu Institute of Technology , 2004 , 16(1) : 35-39);

[0040] 2) Add 1.3-symmetric dithiosemicarbazide (1.00 g, 10 mmol) and 2-acetylpyrazine (2.40 g, 20 mmol) into a flask containing 50 mL of ethanol at room temperature, and then add 0.35 mL of glacial acetic acid dropwise , Mixed and then stirred and refluxed for 4h, cooled, filtered, and the precipitate was recrystallized with ethanol and dried in vacuum to obtain an orange-red powder with a yield of about 75%. Elemental analysis results measured value: C 49.87, H 4.18, N 35.78; calculated value C 13 h 13 N 8 S (%): C 49.97, H 4.09, N 35.90; IR (KBr, cm -1 ): ν (C=N) 1614 cm -1 , ν (C=S) 852 cm -1 , ν (N=N) 1104 cm -1 .

[0041] The preparation...

Embodiment 2

[0044] The preparation method of two (2-acetylpyrazinyl) thiobisemicarbazones, it comprises the steps:

[0045] 1) Synthesize the required 1.3-symmetric dithiosemicarbazide according to the literature method (see Sheng Mei, Jiang Yanqing, Lu Zhengwei, Journal of Jiangsu Institute of Technology , 2004 , 16(1) : 35-39);

[0046] 2) Add 1.3-symmetric dithiosemicarbazide (1.00 g, 10 mmol) and 2-acetylpyrazine (3.00 g, 25 mmol) into a flask containing 50 mL of methanol at room temperature, and then add 0.35 mL of glacial acetic acid dropwise , Mixed and then stirred and refluxed for 4h, cooled, filtered, and the precipitate was recrystallized with methanol and then vacuum-dried to obtain an orange-red powder with a yield of about 81%. Elemental analysis results measured value: C 49.87, H 4.18, N 35.78; calculated value C 13 h 13 N 8 S (%): C 49.97, H 4.09, N 35.90; IR (KBr, cm -1 ): ν (C=N) 1614 cm -1 , ν (C=S) 852 cm -1 , ν (N=N) 1104 cm -1 .

[0047] The prepara...

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