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抗疟先导化合物的再利用用于癌症治疗:探索 N-肉桂酰基-氨基吖啶类化合物的抗增殖作用。

Repurposing antiplasmodial leads for cancer: Exploring the antiproliferative effects of N-cinnamoyl-aminoacridines.

机构信息

LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Portugal.

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Portugal.

出版信息

Bioorg Med Chem Lett. 2024 Oct 1;111:129894. doi: 10.1016/j.bmcl.2024.129894. Epub 2024 Jul 21.

Abstract

Drug repurposing and rescuing have been widely explored as cost-effective approaches to expand the portfolio of chemotherapeutic agents. Based on the reported antitumor properties of both trans-cinnamic acids and quinacrine, an antimalarial aminoacridine, we explored the antiproliferative properties of two series of N-cinnamoyl-aminoacridines recently identified as multi-stage antiplasmodial leads. The compounds were evaluated in vitro against three cancer cell lines (MKN-28, Huh-7, and HepG2), and human primary dermal fibroblasts. One of the series displayed highly selective antiproliferative activity in the micromolar range against the three cancer cell lines tested, without any toxicity to non-carcinogenic cells.

摘要

药物重定位和再利用已被广泛探索,作为一种经济有效的方法来扩大化疗药物的组合。基于报道的反式肉桂酸和抗疟喹啉的抗肿瘤特性,我们研究了最近被确定为多阶段抗疟先导化合物的两个系列 N-肉桂酰基-吖啶的增殖抑制特性。这些化合物在体外针对三种癌细胞系(MKN-28、Huh-7 和 HepG2)和人原代真皮成纤维细胞进行了评估。其中一个系列在测试的三种癌细胞系中显示出高选择性的微摩尔范围的增殖抑制活性,而对非致癌细胞没有任何毒性。

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