- Synthesis, characterization, and antitumor activity of novel tumor-targeted platinum(IV) complexes
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Four tumor-targeted platinum(IV) complexes with ammonia and cyclohexylamine as the carrier groups and biotin as the axial group were designed, synthesized, and characterized. In vitro evaluation of the antitumor activity of complexes C1–C4 against lung cancer cells (A549), liver cancer cells (SMMC-7721), breast cancer cells (MCF-7), and colon cancer cells (SW480) was carried out. Complex C3 had the best cellular activity. Compared with cisplatin, complex C3 showed good anticancer activity against A549 cell line,complex C3 (6.34±0.44) is 3 times more cytotoxic than cisplatin (19.40±0.71),and against MCF-7 cell line complex C3 (4.22±0.11) is 5.4 times more cytotoxic than cisplatin (22.96±0.58), and against SW480 cell line complex C3 (6.65±0.60) is 3.4 times more cytotoxic than cisplatin (23.15±0.22). (Table 1) Axial chloride increased the redox power of complex C3 to increase the intercellular accumulation and the introduction of mixed amine had the ability to overcome cisplatin resistance. Complex C3 works best on MCF-7, then SW480, A549, and SMMC-7721. Thus, complex C3 is targeted by the axial introduction of biotin.
- Cong, Yanwei,Gao, Chuanzhu,Jia, Chunyan,Liao, Xiali,Pu, Shaoping,Yang, Bo,Zhang, Xinzhong,Zhong, Yunshuang
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- Preparation method and application of novel Pt(IV) complex with tumor targeting function
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The invention discloses a novel Pt(IV) complex with a tumor targeting function. The complex has a structure represented by the formula (I) or the formula (II). The invention discloses a preparation method of the novel Pt(IV) complex. According to the preparation method, an asymmetric ammonia ligand of a Satraplatin carrier group is maintained, a biotin ligand with a targeting function is introduced into one axial end, chloride is introduced into the other end so as to reduce the negative value of the redox potential of the platinum complex, the reducing power is increased at the same time; ora hydroxyl group of the other end is maintained, thus after the Pt(IV) complex enters a human body, the Pt(IV) complex can preferably combine with a reducing agent in the human body, and the Pt(IV) complex is reduced to obtain Pt(II) complex so as to treat the tumors. The provided Pt(IV) complex has antitumor activity on specific tumors, and the toxic effect and side effect are reduced. At the same time, the raw materials are cheap and easily available, the preparation method is simple and is easy to perform, the conditions are mild, the operation is easy, and the preparation method is suitable for large scale production. Z is Cl.
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- A compound with anticancer activity and its preparation method
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The invention provides a compound having anticancer activity, which is obtained by cooperation of Norabieta cantharidin and platinum (IV) and modification of a piperazine derivative. The compound is characterized in that a Norabieta cantharidin piperazine derivative ligand is introduced, thereby cytotoxicity of a platinum (IV) compound is reduced, and high antineoplastic activity is provided. The result of the cytotoxicity experiments shows that the provided platinum (IV) compound has less destruction to normal mice fibroblast L929, but has good killing effect to cancer cells such as human breast cancer MCF-7 cell, human cervical carcinoma HeLa cell and human lung adenocarcinoma A549 cell, so that the compound having anticancer activity is capable of reducing the system toxicity and having equal anticancer activity with cisplatin. The compound having anticancer activity has good killing effect by aiming at cisplatin resistance human lung adenocarcinoma A549/DDP cell. Therefore, the toxicity is reduced, the cisplatin resistance can be reversed, and anticancer effect of the platinum medicines can be increased.
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Paragraph 0107; 0108
(2017/02/28)
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- Chemical substance with anticancer activity and preparation method and application thereof
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The invention discloses a chemical substance with anticancer activity and a preparation method and application thereof, belongs to the technical field of chemically-synthesized medicine, and aims to provide the chemical substance with low cytotoxicity, low drug resistance and high anticancer activity. The chemical substance is a compound as shown in formula (I), a compound as shown in formula (II) or the mixture of the compound as shown in formula (I) and the compound as shown in formula (II). The chemical substance has the advantages that the chemical substance is obtained by the mating reaction of artesunate and a platinum (IV) compound, the cytotoxicity of the platinum (IV) compound is lowered by introducing the artesunate ligand, the anticancer cavity of the platinum (IV) compound is increased, and the chemical substance is low in drug resistance and widely applicable to the preparation of anticancer medicine.
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Paragraph 0089; 0090; 0095
(2016/10/27)
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- Crystal and Molecular Structures of Asymmetric cis- and trans-Platinum(II/IV) Compounds and Their Reactions with DNA Fragments
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The asymmetrically substituted platinum(II) complexes cis-Pt(NH3)(c-C5H11NH2)Cl 2 and trans-Pt(NH3)(c-C6H11-NH2)Cl 2 have been synthesized and their crystal structures have been determined. Crystals of cis-Pt(NH3)(c-C6H11NH2)Cl 2 (1) are orthorhombic, space group Pbca (no. 61) with a = 10.1994(12), b = 10.494(2), c = 18.826(2) ?, Z = 8. The structure refinement converged to R1 = 0.0518 and wR2 = 0.1143. Crystals of trans-Pt(NH3)(c-C6H11NH2)Cl 2 (2) are monoclinic, space group P21/c (no. 14) with a = 12.141(3), b = 6.0965(9), c = 19.864(3) ?, β= 118.71(2)°, Z = 4. The structure refinement converged to R1 = 0.0711 and wR2 = 0.1846. In addition, the Pt(IV) analogues with axial hydroxide ligands have been synthesized. Also the corresponding bis(carboxylato)-platinum(IV) compound of formula trans,cis,cis-Pt(NH3)(c-C6H11NH 2)Cl2(OOCCH3)2 has been obtained by conversion of the hydroxide with acetic anhydride. Reactions of these platinum complexes with 9-methylhy-poxanthine and guanosine-5′-monophosphate (5′-GMP) have been studied in significant detail. The course of the reactions was followed by NMR spectroscopy, and 1H and 195Pt techniques were used to identify the formation of the products. It was found that the Pt(II) compounds easily react with the bases at the N7 position, whereas the Pt(IV) compounds react very slowly (for trans,cis,cis-Pt(NH3)(c-C6H11NH 2)Cl2(OOCCH3)2) or not at all (for trans,trans,trans-Pt(NH3)(c-C6H11NH 2)Cl2(OH)2). Only in the presence of glutathione does a reaction of the latter with 5′-GMP takes place. In this case a major product was found to be the reduced trans-Pt(II) complex with one molecule of 5′-GMP and one molecule of S-bonded glutathione.
- Talman, Eduard G.,Brüning, Wolfgang,Reedijk, Jan,Spek, Anthony L.,Veldman, Nora
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p. 854 - 861
(2008/10/09)
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- Carboxylation of kinetically inert platinum(IV) hydroxy complexes. An entrée into orally active platinum(IV) antitumor agents
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Carboxylation of hydroxide coordinated to Pt(IV) by anhydrides, pyrocarbonates, and isocyanates to form the corresponding Pt(IV) carboxylates, carbonates, and carbamates is described. For example, the acylation with acetic anhydride of (OC-6-33)-amminedichloro(cyclohexanamine)dihydroxyplatinum(IV) leads to formation of (OC-6-43)-bis(acetato-O)amminedichloro(cyclohexanamine)platinum(IV) (JM-216) in 60% yield. This compound is currently in worldwide clinical trials as an orally active antitumor agent. Pt(IV) dicarbonates and dicarbamates are prepared similarly by reaction of a Pt(IV) hydroxide with a pyrocarbonate or isocyanate. The carboxylation reaction can be used to prepare molecules containing ligands with pendant functional groups that would be difficult to introduce by substitution reactions. Thus (OC-6-43)-amminedichloro(cyclohexanamine)bis((methylthio)acetato-O)platinum(IV) was prepared, which was oxidized to the corresponding sulfoxide (OC-6-43)-amminedichloro-(cyclohexanamine)bis((methylsulfinyl)acetato-O) platinum(IV). Finally, unsymmetrical carboxylate complexes may be obtained by reaction of a binary mixture of two electrophiles with a Pt(IV) hydroxide followed by chromatographic separation of the carboxylation products. A simplified synthesis of the K[PtIICl3NH3] in 55% yield from cisplatin is also reported. This improves the availability of molecules of the general formula cis-PtII-Cl2AA′ (A, A′ = ammine, amine) which are critical intermediates in the multistep synthesis of the Pt(IV) carboxylates having antitumor activity.
- Giandomenico, Christen M.,Abrams, Michael J.,Murrer, Barry A.,Vollano, Jean F.,Rheinheimer, Melanie I.,Wyer, Sandra B.,Bossard, Gerald E.,Higgins III, John D.
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p. 1015 - 1021
(2008/10/08)
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