顺式-乙二酸-(反式-1,2-二甲胺基环丁烷)合铂(Ⅱ)的合成、表征及抗肿瘤活性
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摘要
设计并合成了一种洛铂衍生物顺式-乙二酸-(反式-1,2-二甲胺基环丁烷)合铂(Ⅱ)(C8H14O4N2Pt)。采用元素分析、质谱(ESI-MS)、红外光谱(IR)、核磁共振氢谱(1H NMR)对其化学组成和结构进行了确认和表征,用高效液相色谱(HPLC)测定其在水溶液中的稳定性,并用MTS法对其进行抗肿瘤活性评价。结果表明化合物结构与理论一致,在水溶液中比较稳定,对5种常见肿瘤细胞具有明显的抑制作用。
A derivative of lobaplatin, [trans-1,2-bis(aminomethyl)cyclobutane]oxalatoplatinum(Ⅱ), was synthesized and characterized by elemental analysis, ESI-MS, IR and 1 H-NMR. The stability in water was measured by HPLC, and the in vitro anticancer activity was tested by MTS method. The results show that the compound is stable in water and exhibits obvious inhibitory effect on 5 tumor cell lines.
A derivative of lobaplatin, [trans-1,2-bis(aminomethyl)cyclobutane]oxalatoplatinum(Ⅱ), was synthesized and characterized by elemental analysis, ESI-MS, IR and 1 H-NMR. The stability in water was measured by HPLC, and the in vitro anticancer activity was tested by MTS method. The results show that the compound is stable in water and exhibits obvious inhibitory effect on 5 tumor cell lines.
引文
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[2]ROSENBERG B.Platinum complexes for the treatment of cancer[J].Interdisciplinary science reviews,1978,3(2):134-147.
[3]MOGHADDAS S,MAJMUDAR P,MARIN R,et al.Phosphaplatins,next generation platinum antitumor agents:A paradigm shift in designing and defining molecular targets[J].Inorganica chimica acta,2012,393(12):173-181.
[4]WHEATE N J,WALKER S,CRAIG G E,et al.The status of platinum anticancer drugs in the clinic and in clinical trials[J].Dalton transactions,2010,39(35):8097-8340.
[5]丛艳伟,陈宏,栾春芳,等.((R)-(-)-1,2-丙二胺)(1,3-丙二酸)合铂(II)的合成、表征及抗肿瘤活性研究[J].贵金属,2014,35(4):26-29.CONG Y W,CHEN H,LUAN C F,et al.Synthesis,characterization and anticancer activity of((R)-(-)-1,2-diaminepropane)(1,3-malonate)Platinum(II)[J].Precious metals,2014,35(4):26-29.
[6]LI S,HUANG H,LIAO H,et al.Phase I clinical trial of the novel platin complex dicycloplatin:clinical and pharmacokinetic results[J].International journal of clinical pharmacology and therapeutics,2013,51(2):96-105.
[7]WAGSTAFF A J,BROWN S D,HOLDEN M R,et al.Cisplatin drug delivery using gold-coated iron oxide nanoparticles for enhanced tumour targeting with external magnetic fields[J].Inorganica chimica acta,2012,393(12):328-333.
[8]MCKEAGE M J.Lobaplatin:A new antitumour platinum drug[J].Expert opinion on investigational drugs,2001,10(1):119-128.
[9]HUANG X E,WEI G L,HUO J G,et al.Intrapleural or intraperitoneal lobaplatin for treatment of patients with malignant pleural effusion or ascites[J].Asian pacific journal of cancer prevention apjcp,2013,14(4):2611-2614.
[10]KIRPENSREIJN J,TESKE E,KIK M,et al.Lobaplatin as an adjuvant chemotherapy to surgery in canine appendicular osteosarcoma:a phase II evaluation[J].Anticancer research,2002,22(5):2765-2770.
[11]XIE C Y,XU Y P,JIN W,et al.Antitumor activity of lobaplatin alone or in combination with antitubulin agents in non-small-cell lung cancer[J].Anti-cancer drugs,2012,23(7):698-705.
[12]方成玲,金描真,林晓泉,等.洛铂在不同温度生理盐水中的稳定性[J].中国新药杂志,2012,21(19):2321-2325.FANG C L,JIN M Z,LIN X Q,et al.Stability of lobaplatin in saline at different temperatures[J].Chinese journal of new drugs,2012,21(19):2321-2325.
[13]杨水艳,谢笑天,叶青松,等.铂类抗癌配合物的高效液相色谱法研究进展[J].贵金属,2011,32(3):89-97.YANG S Y,XIE X T,YE Q S,et al.Research progress of the HPLC method for anti-cancer platinum complexes[J].Precious metals,2011,32(3):89-97.
[14]KOK S H,GAMBARI R,CHUI C H,et al.Paradoxical proliferative potential of iron(II)sulphate on cancer cells after the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium(MTS)assay[J].International journal of molecular medicine,2007,19(6):971-975.