New in vitro highly cytotoxic platinum and palladium cyanoximates with minimal side effects in vivo.
New in vitro highly cytotoxic platinum and palladium cyanoximates with minimal side effects in vivo.
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DOI：
10.1016/j.jinorgbio.2020.111082
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发表时间：
2020-07
影响因子：
3.9
通讯作者：
Gerasimchuk N
中科院分区：
文献类型：
--
作者：
Dannen SD;Cornelison L;Durham P;Morley JE;Shahverdi K;Du J;Zhou H;Sudlow LC;Hunter D;Wood MD;Berezin MY;Gerasimchuk N
合成了具有生物活性的二价钯、铂配合物，分别与2-肟基-2-氰基-N，N′-二乙基乙酰胺和2-肟基-2-氰基-N-吡咯烷-乙酰胺配体H（DECO）和H（PyrCO）配体H（DECO）配体H（PyrCO）配体。结构揭示平面顺式几何的研究复合物。新鲜获得的Pt（DECO）2、Pd（DECO）2、Pt（PyrCO）2和Pd（PyrCO）2络合物用于使用两种不同病因人类癌细胞系HeLa和WiDr细胞的体外细胞毒性测定。研究的化合物显示出顺铂或更高的细胞毒性水平。还在健康C57 BL/6小鼠中体内测试了Pt（DECO）2。以三种不同剂量（0、7.5、15 mg/kg，腹膜内注射一次/周）给予复合物，共8周。与对照组相比，给药组小鼠的动物体重未观察到变化。红细胞、白细胞和血红蛋白水平均在正常水平范围内，表明骨髓毒性较低。从给药动物心脏的组织学评价中观察到的心脏毒性可忽略不计。尾神经传导速度（NCV）和神经组织形态计量学的结果表明，Pt（DECO）2对周围神经无影响。然而，该复合物诱导了一定的肝毒性，并导致IL-6（一种促炎细胞因子）的升高。总的来说，Pt（DECO）2显示出最小的体内毒性，因此为未来在癌症动物模型中的测试提供了有希望的候选物。
Several biologically active bivalent Pd and Pt complexes with two structurally similar cyanoxime ligands abbreviated as H(DECO): 2-oximino-2-cyano-N,N′-diethylacetamide, and H(PyrCO): 2-oximino-2-cyan-N-pyrrolidine acetamide were synthesized and characterized using spectroscopic methods, thermal analysis and X-ray crystallography. Structures revealed planar cis-geometry of studied complexes. Freshly obtained Pt(DECO)2, Pd (DECO)2, Pt(PyrCO)2 and Pd(PyrCO)2 complexes were used in for in vitro cytotoxicity assays using two different etiology human cancer cell lines HeLa and WiDr cells. Investigated compounds showed cytotoxicity levels at or above cisplatin. Pt(DECO)2 was also tested in vivo in healthy C57BL/6 mice. The complex was administered at three different dosage (0, 7.5, 15 mg/kg, i.p. once/week), over a total period of 8 weeks. No changes were observed in the animal weight in the treated mice compared to the control dextrose-treated group. The levels of erythrocytes, leukocytes, and hemoglobin were within the normal level suggesting low myelotoxicity. Negligible cardiotoxicity was observed from the histological evaluation of the hearts from the treated animals. Results from the tail nerve conduction velocity (NCV) and nerve histomorphometry suggested no impact of Pt(DECO)2 on peripheral nerves. The complex, however, induced certain hepatotoxicity and lead to the elevation of IL-6, a pro-inflammatory cytokine. Overall, Pt(DECO)2 showed minimal in vivo toxicity, thus presenting a promising candidate for future testing in animal models of cancer.
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DOI：
10.1002/jcsm.12267
发表时间：
2018-04
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Daly LE;Ní Bhuachalla ÉB;Power DG;Cushen SJ;James K;Ryan AM
通讯作者：
Ryan AM
影响因子：
4.6
作者：
Boehmerle W;Huehnchen P;Peruzzaro S;Balkaya M;Endres M
通讯作者：
Endres M
影响因子：
3.7
作者：
Marmiroli P;Riva B;Pozzi E;Ballarini E;Lim D;Chiorazzi A;Meregalli C;Distasi C;Renn CL;Semperboni S;Morosi L;Ruffinatti FA;Zucchetti M;Dorsey SG;Cavaletti G;Genazzani A;Carozzi VA
通讯作者：
Carozzi VA
影响因子：
3.6
作者：
Grigorian A;O'Brien CB
通讯作者：
O'Brien CB
影响因子：
2.7
作者：
Hull, M;Strauss, S;Bauer, J
通讯作者：
Bauer, J