Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells.
Aromatic Linkers Unleash the Antiproliferative Potential of 3-Chloropiperidines Against Pancreatic Cancer Cells.
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芳香族接头释放3-氯哌啶类化合物对胰腺癌细胞的抗增殖潜能。
DOI：
10.1002/cmdc.202000457
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发表时间：
2020-11-04
期刊：
影响因子：
3.4
通讯作者：
Gatto B
中科院分区：
文献类型：
--
作者：
Helbing T;Carraro C;Francke A;Sosic A;De Franco M;Gandin V;Göttlich R;Gatto B
在这项研究中，我们描述了一组含有刚性芳香族连接体结构的双-3-氯哌啶(B-−CEP)的合成和生物活性。对合成策略的改进也使得在芳香族支架上合成了含有三个活性间氯哌啶部分的先导化合物Tris-3-氯哌啶(Tri-CEP)。B-−CEPS的结构-反应性关系分析表明，反应单元的排列影响DNA烷基化活性，同时也揭示了芳香族体系的电子密度与与生物相关的亲核剂的反应活性之间的相关性，无论是在分离的DNA上还是在癌细胞中。有趣的是，所有芳香族3-氯哌啶类化合物对胰腺癌细胞的2D和3D培养都表现出明显的细胞毒性和趋向性。因此，新的芳香族3-氯哌啶类化合物似乎是进一步开发以芥子为基础的针对胰腺癌的抗癌药物的有力竞争者。与芥末一样敏锐：旨在提高芥子基DNA烷化剂治疗潜力的芳香族3-氯哌啶类化合物已经合成并进行了评估。这些小分子在2D和3D培养中对BxPC-3胰腺癌细胞表现出明显的抗增殖作用，从而为进一步开发抗胰腺肿瘤的可持续化疗药物提供了有前途的候选药物。
In this study, we describe the synthesis and biological evaluation of a set of bis‐3‐chloropiperidines (B−CePs) containing rigid aromatic linker structures. A modification of the synthetic strategy also enabled the synthesis of a pilot tris‐3‐chloropiperidine (Tri‐CeP) bearing three reactive meta‐chloropiperidine moieties on the aromatic scaffold. A structure–reactivity relationship analysis of B−CePs suggests that the arrangement of the reactive units affects the DNA alkylating activity, while also revealing correlations between the electron density of the aromatic system and the reactivity with biologically relevant nucleophiles, both on isolated DNA and in cancer cells. Interestingly, all aromatic 3‐chloropiperidines exhibited a marked cytotoxicity and tropism for 2D and 3D cultures of pancreatic cancer cells. Therefore, the new aromatic 3‐chloropiperidines appear to be promising contenders for further development of mustard‐based anticancer agents aimed at pancreatic cancers. As keen as mustard: Aromatic 3‐chloropiperidines designed to improve the therapeutic potential of mustard‐based DNA alkylating agents have been synthesized and evaluated. These small molecules exhibited a marked anti‐proliferative effect preferentially against BxPC‐3 pancreatic adenocarcinoma cells in 2D and 3D cultures, thus demonstrating themselves to be promising candidates for the further development of sustainable chemotherapeutics active against pancreatic tumors.
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影响因子：
3.5
作者：
Zuravka, Ivonne;Roesmann, Rolf;Gatto, Barbara
通讯作者：
Gatto, Barbara
影响因子：
4.6
作者：
Gandin, Valentina;Ceresa, Cecilia;Marzano, Cristina
通讯作者：
Marzano, Cristina
DOI：
10.1039/p29910001933
发表时间：
1991-12-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2
影响因子：
--
作者：
OCONNOR, CJ;DENNY, WA;MCLENNAN, DJ
通讯作者：
MCLENNAN, DJ
影响因子：
78.5
作者：
Chabner, BA;Roberts, TG
通讯作者：
Roberts, TG
影响因子：
3.4
作者：
Zuravka, Ivonne;Roesmann, Rolf;Goettlich, Richard
通讯作者：
Goettlich, Richard