Platinum (II) coordination complex and preparing method and application thereof

A technology of complexes and drugs, which is applied in platinum-group organic compounds, platinum-based organic compounds, pharmaceutical formulations, etc., can solve problems such as cross-resistance, toxic and side effects, and achieve mild release activity and good in vitro inhibitory activity.

Active Publication Date: 2016-06-29
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing platinum drugs also have many defects, typically severe toxic side effects and cross-drug resistance

Method used

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  • Platinum (II) coordination complex and preparing method and application thereof
  • Platinum (II) coordination complex and preparing method and application thereof
  • Platinum (II) coordination complex and preparing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0015] The preparation method of novel platinum (II) complex of the present invention is shown in reaction formula (I):

[0016]

[0017] Potassium tetrachloroplatinate coordinates with ammonia or (R,R)-cyclohexanediamine in the presence of potassium iodide to obtain intermediate 2 or 2', and then removes iodide ion by silver nitrate under light-shielding conditions, and then reacts with The complex represented by the formula (1) is obtained by reacting the sodium salt of ursodeoxycholic acid or oleanolic acid or an oleanolic acid derivative.

[0018] The pharmaceutical use of the novel platinum (II) complexes of the present invention is that the novel platinum (II) complexes are used for the treatment of malignant tumors, and they can treat human liver cancer cells HepG2, human gastric cancer cells SGC7901, human lung cancer cells A549 and human Colon cancer cell HCT-116 showed good inhibitory activity in vitro.

Embodiment 1

[0019] Embodiment 1. Preparation of oleanolic acid diammine platinum (compound 1)

[0020]

[0021] Diiododiammine platinum (0.5g, 1mmol) and silver nitrate (0.3g, 2mmol) were dissolved in 100ml of water, stirred and reacted at 40°C for 24h in the dark, and the clear solution was filtered. Then add the prepared tetrahydrofuran / water mixed solution of sodium oleanolic acid (1.0g, 2mmol) into the above reaction solution, stir and react in the dark at 40°C for 24h, filter, concentrate the filtrate to about 10ml, cool, and have a white The solid was precipitated, filtered, and recrystallized from tetrahydrofuran to obtain a white product with a yield of 40%. 1 HNMR (DMSO-d 6 ,500MHz):δ5.30-5.28(m,2H,2C H =C),4.20(br,6H,2N H 3 ),3.24-3.18(m,2H,2C 3 - H ),2.90-2.86(m,2H,2C 18 - H ),1.14(s,6H,2C H 3 ),0.99(s,6H,2C H 3 ),0.93(s,6H,2C H 3 ),0.91(s,6H,2C H 3 ),0.90(s,6H,2C H 3 ),0.78(s,6H,2C H 3 ),0.72(s,6H,2C H 3 )cm -1 ;ESI-MS:1140.5[M+H] + .

Embodiment 2

[0022] Embodiment 2. Preparation of oleanolic acid cyclohexanediamine platinum (compound 2)

[0023]

[0024] Prepared by reacting diiodocyclohexanediamine platinum with oleanolic acid sodium salt in the presence of silver nitrate, the method is the same as that of Example 1, and the yield is 29%. 1 HNMR (DMSO-d 6 ,500MHz):δ5.96(br,2H,N H 2 ),5.30-5.28(m,2H,2C H =C),5.25(br,2H,N H 2 ),3.23-3.19(m,2H,2C 3 - H ),2.91-2.86(m,2H,2C 18 - H ),1.14(s,6H,2C H 3 ),0.99(s,6H,2C H 3 ),0.93(s,6H,2C H 3 ),0.91(s,6H,2C H 3 ),0.90(s,6H,2C H 3 ),0.78(s,6H,2C H 3 ),0.72(s,6H,2C H 3 )cm -1 ;ESI-MS: 1250.7[M+H] + .

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Abstract

The invention discloses a platinum (II) coordination complex and a preparing method and application thereof. The preparing method includes the steps that active natural products such as oleanolic acid and ursodesoxycholic acid and derivatives of the active natural products serve as ligand; potassium tetrachloroplatinate(II) and ammonia or (R,R)-cyclohexanediamine are subjected to coordination reaction under the condition of potassium iodide, then iodide ions are removed through silver nitrate under the light shielding condition, and the mixture and sodium salt of ursodesoxycholic acid or oleanolic acid or the derivatives of oleanolic acid are reacted to obtain the product. The platinum (II) coordination complex has the good in-vitro antitumor activity, and can be applied to preparing medicine for treating malignant tumor.

Description

technical field [0001] The invention relates to a novel platinum (II) complex with oleanolic acid, ursodeoxycholic acid and other active natural products and derivatives thereof as ligands, a preparation method and its application in the treatment of malignant tumors. Background technique [0002] Antitumor platinum drugs represented by cisplatin and oxaliplatin are the first-line drugs for clinical cancer treatment. In the chemotherapy regimens of many types of tumors, anti-tumor platinum drugs play an indispensable role through their single administration or in combination with other anti-cancer drugs. However, the existing platinum drugs also have many defects, typically severe toxic side effects and cross-drug resistance. In order to overcome these defects, researchers have designed and synthesized a variety of non-classical platinum (II) complexes, such as transplatinum, multinuclear platinum, tetravalent platinum and so on. It is also an effective research strategy t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F15/00A61K31/282A61K31/555A61P35/00
CPCC07F15/0093
Inventor 房雷
Owner SOUTHEAST UNIV
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