Platinum (IV) Derivatives with Cinnamate Axial Ligands as Potent Agents Against Both Differentiated and Tumorigenic Cancer Stem Rhabdomyosarcoma Cells

Zajac Juraj; Novohradsky Vojtech; Markova Lenka; Brabec Viktor; Kasparkova Jana

摘要

Abstract > To design an anticancer drug capable of inhibiting not only the proliferation of the differentiated tumor cells but also reducing the tumorigenic capability of cancer stem cells (CSCs), the new Pt IV prodrugs with axial cinnamate ligands were synthesized. We demonstrate their superior antiproliferative activity in monolayer and 3D spheroid antiproliferative activity tests using panel of cancer cell lines. An outstanding activity was found against rhabdomyosarcoma cells, one of the most problematic and poorly treatable pediatric tumors. The results also suggest that the released Pt II compound inhibits antiproliferative activity of cancer cells by DNA‐damage mediated mechanism; the released cinnamic acid can trigger processes leading to differentiation, making the CSCs more sensitive to killing by the platinum part of the complex. Pt IV complex with axial cinnamate ligands is the first Pt IV prodrug capable of overcoming CSCs resistance and induce death in both CSCs and bulk cancer. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> > 设计一种能够抑制分化的肿瘤细胞的增殖，而且降低癌症干细胞（CSCs），新的PT的致瘤能力的抗癌药物 iv </ sup> 合成具有轴向肉桂酸酯配体的前药。我们在单层和3D球形抗增殖活性试验中展示了它们在单层和3D球形抗增殖活性试验中的优异抗增殖活性。针对横纹肌肉瘤细胞，最有问题且可治疗不良的儿科肿瘤之一，发现了出色的活性。结果还表明发布的PT ii </ sup> 化合物通过DNA损伤介导机制抑制癌细胞的抗增殖活性;释放的肉桂酸可以触发导致分化的过程，使CSC对复合物的铂部分杀死更敏感。 Pt. iv </ sup> 与轴向肉桂酸酯配体的复合物是第一个PT iv </ sup> 能够克服CSCs抗性并在CSC和散装癌中诱导死亡的前药。 </ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-19011/'>《Angewandte Chemie》</a> <b style="margin: 0 2px;">|</b><span>2020年第8期</span><b style="margin: 0 2px;">|</b><span>共7页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Zajac Juraj&option=202" target="_blank" rel="nofollow">Zajac Juraj;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Novohradsky Vojtech&option=202" target="_blank" rel="nofollow">Novohradsky Vojtech;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Markova Lenka&option=202" target="_blank" rel="nofollow">Markova Lenka;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Brabec Viktor&option=202" target="_blank" rel="nofollow">Brabec Viktor;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Kasparkova Jana&option=202" target="_blank" rel="nofollow">Kasparkova Jana;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Institute of BiophysicsCzech Academy of SciencesKralovoposlka 135 CZ-61265 Brno Czech Republic;</p> <p>Institute of BiophysicsCzech Academy of SciencesKralovoposlka 135 CZ-61265 Brno Czech Republic;</p> <p>Institute of BiophysicsCzech Academy of SciencesKralovoposlka 135 CZ-61265 Brno Czech Republic;</p> <p>Institute of BiophysicsCzech Academy of SciencesKralovoposlka 135 CZ-61265 Brno Czech Republic;</p> <p>Institute of BiophysicsCzech Academy of SciencesKralovoposlka 135 CZ-61265 Brno Czech Republic;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1188.html" title="应用化学">应用化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=antitumor agents&option=203" rel="nofollow">antitumor agents;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cancer&option=203" rel="nofollow">cancer;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=cancer stem cells&option=203" rel="nofollow">cancer stem cells;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=drug design&option=203" rel="nofollow">drug design;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=platinum&option=203" rel="nofollow">platinum;</a> </p> <div class="translation"> 机译：抗肿瘤剂;癌症;癌症干细胞;药物设计;铂金; 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molecule, isolated nucleic acid, cell containing the same, recombinant non-human animal, pharmaceutical composition, vaccine composition, processes for identifying or measuring or detecting a cancer antigen, an antigen from an infectious disease agent, a ligand, and a receptor in a sample. to be tested, kits for detecting a cancer antigen, an infectious disease agent antigen, a cell receptor for an infectious disease agent, a ligand, and a cancer antigen, diagnostic processes or testing for the presence of or a predisposition for the development of a cancer by the increased presence of a cancer antigen, and for the presence of an infectious disease, treatment or prevention of a cancer by the presence of a cancer antigen, of an infectious disease typified by the presence of an antigen infectious disease agent, and a disease caused by an infectious disease agent that binds to a cell receptor, processes for modulating activity of a first member of a binding pair,</a> <b>[P]</b> . <span> 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initial;"> <span>机译：包含双黄药-铂络合物的稳定，有效，无毒的广谱抗肿瘤药，对小细胞肺癌和大肠癌特别有效 </span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130453333507.html">Identification of differentiation factor receptors which inhibit the tumorigenicity of neuroblastoma cells in a ligand-independent manner</a> <b>[P]</b> . <span> 外国专利：  US5789187A </span> <span> . 1998-08-04</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：鉴定以配体非依赖性方式抑制神经母细胞瘤细胞致瘤性的分化因子受体 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" 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