Synthesis and cytotoxicity of some D-mannose click conjugates with aminobenzoic acid derivatives
Synthesis and cytotoxicity of some D-mannose click conjugates with aminobenzoic acid derivatives
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DOI：
10.1016/j.carres.2012.08.001
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发表时间：
2012-11-01
影响因子：
3.1
通讯作者：
Petrus, Ladislav
中科院分区：
文献类型：
--
作者：
Hradilova, Ludmila;Polakova, Monika;Petrus, Ladislav
通过 Cu(I) 催化叠氮-炔环加成反应，合成了两套由 D-甘露糖衍生物和邻位、间位和对位取代的苯甲酸酯通过三唑环互连获得的新缀合物。所有合成的化合物均针对具有/不具有多药耐药表型的七种癌细胞系以及非肿瘤 MRC-5 和 BJ 成纤维细胞进行了体外细胞毒活性测试。 4-氨基苯甲酸丁酯 6c 在所有测试的化合物中显示出最高的活性，但它仅对 K562 骨髓性白血病细胞有活性。 N-糖基三唑缀合物，无论是甘露糖部分乙酰化的还是非乙酰化的，几乎完全没有活性。相反，一些乙酰化O-糖基缀合物表现出细胞毒活性，该活性是细胞系依赖性的，并且受到苯甲酸取代位置及其酯烷基链长度的强烈影响；最有效的化合物是与间位取代的苯甲酸辛酯缀合的乙酰化甘露糖苷。然而，脱乙酰化导致糖苷亲水性增加，几乎完全消除了它们的细胞毒性效力。 (C) 2012 Elsevier Ltd. 保留所有权利。
Two sets of new conjugates obtained from D-mannose derivatives and o-, m-, and p-substituted benzoic acid esters interconnected through a triazole ring were synthesized by Cu(I) catalyzed azide-alkyne cycloaddition. All synthesized compounds were tested for their in vitro cytotoxic activity against seven cancer cell lines with/without multidrug resistance phenotype as well as non-tumor MRC-5 and BJ fibroblasts. Butyl ester of 4-aminobenzoic acid 6c showed the highest activity among all tested compounds, however, it was active only against K562 myeloid leukemia cells. N-Glycosyltriazole conjugates, both acetylated and nonacetylated at mannose moiety, were almost completely inactive. In contrast, some of the acetylated O-glycosyl conjugates showed cytotoxic activity which was cell line dependent and strongly affected by position of benzoic acid substitution as well as a length of its ester alkyl chain; the most potent compound was acetylated mannoside conjugated with octyl ester of m-substituted benzoic acid. However, deacetylation resulting in hydrophilicity increase of the glycosides almost completely abolished their cytotoxic potency. (C) 2012 Elsevier Ltd. All rights reserved.