Influence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamides.
Influence of Terminal Functionality on the Crystal Packing Behaviour and Cytotoxicity of Aromatic Oligoamides.
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DOI：
10.3389/fchem.2021.709161
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发表时间：
2021
影响因子：
5.5
通讯作者：
Pike SJ
中科院分区：
文献类型：
--
作者：
Delfosse P;Seaton CC;Male L;Lord RM;Pike SJ
本文报道了三种以吡啶基酰胺为核心，但末端分别为乙酰基（Ac）1、叔丁氧羰基（Boc）2和胺3的芳香低聚酰胺的合成和表征。1-3和2的二甲亚砜（DMSO）溶剂化物（2-DMSO）的单晶X射线衍射分析已经鉴定了一系列分子内和分子间相互作用的存在，包括N-H N、N-H O=C和N-H O=S（CH 3）2氢键相互作用、C-H π相互作用和支持各种滑移堆叠的偏移、面对面堆叠π-π相互作用，在1-3中观察到人字形和共面晶体堆积排列。此外，针对两种人卵巢癌细胞系（A2780和A2780 cisR）、两种人乳腺癌细胞系（MCF-7和MDA-MB-231）和一种非恶性人上皮细胞系（PNT-2）评估了该系列芳香族低聚酰胺的细胞毒性，以研究这些芳香族低聚酰胺的末端官能度对其生物活性的影响。化学敏感性结果突出表明，1和2中末端基团从Ac到Boc的修饰导致对顺铂敏感的卵巢癌细胞系A2780的抗增殖活性增加3倍。3中的胺末端的存在给出了该系列中显示出对顺铂耐药卵巢癌细胞系A2780 cisR的活性的唯一成员。化合物2是该系列的主要候选物，当与非恶性PNT-2细胞相比时，其显示出对A2780癌细胞的高选择性，选择性指数值>4.2。重要的是，该化合物对A2780的选择性更高（参见图1）。PNT-2）比临床铂类药物奥沙利铂多2.6倍，卡铂多1.6倍。
The synthesis and characterization of three aromatic oligoamides, constructed from the same pyridyl carboxamide core but incorporating distinct end groups of acetyl (Ac) 1, tert-butyloxycarbonyl (Boc) 2 and amine 3 is reported. Single crystal X-ray diffraction analysis of 1–3 and a dimethylsulfoxide (DMSO) solvate of 2 (2-DMSO), has identified the presence of a range of intra- and intermolecular interactions including N-H⋯N, N-H⋯O=C and N-H⋯O=S(CH3)2 hydrogen-bonding interactions, C-H⋯π interactions and off-set, face-to-face stacking π-π interactions that support the variety of slipped stack, herringbone and cofacial crystal packing arrangements observed in 1–3. Additionally, the cytotoxicity of this series of aromatic oligoamides was assessed against two human ovarian (A2780 and A2780cisR), two human breast (MCF-7 and MDA-MB-231) cancerous cell lines and one non-malignant human epithelial cell line (PNT-2), to investigate the influence of the terminal functionality of these aromatic oligoamides on their biological activity. The chemosensitivity results highlight that modification of the terminal group from Ac to Boc in 1 and 2 leads to a 3-fold increase in antiproliferative activity against the cisplatin-sensitive ovarian carcinoma cell line, A2780. The presence of the amine termini in 3 gave the only member of the series to display activity against the cisplatin-resistance ovarian carcinoma cell line, A2780cisR. Compound 2 is the lead candidate of this series, displaying high selectivity towards A2780 cancer cells when compared to non-malignant PNT-2 cells, with a selectivity index value >4.2. Importantly, this compound is more selective towards A2780 (cf. PNT-2) than the clinical platinum drugs oxaliplatin by > 2.6-fold and carboplatin by > 1.6-fold.
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影响因子：
3.3
作者：
Nishio, Motohiro
通讯作者：
Nishio, Motohiro
影响因子：
4.3
作者：
Annala, Riia;Suhonen, Aku;Nissinen, Maija
通讯作者：
Nissinen, Maija
影响因子：
3.3
作者：
König, B;Papke, U;Rödel, M
通讯作者：
Rödel, M
影响因子：
3.1
作者：
Suhonen, Aku;Kortelainen, Minna;Nissinen, Maija
通讯作者：
Nissinen, Maija
DOI：
10.1002/anie.199404461
发表时间：
1994-03-03
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH
影响因子：
--
作者：
HAMURO, Y;GEIB, SJ;HAMILTON, AD
通讯作者：
HAMILTON, AD