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新型香豆素-噻唑衍生物作为双靶点EGFR/HDAC1抑制剂的设计、合成及分子模拟：以及抗癌活性测定

Design, synthesis and molecular modeling of new coumarin-thiazole derivatives as dual EGFR/HDAC1 inhibitors: and anticancer assays.

作者信息

Ahmed Eman Y, Elghonemy Mai M, Batran Rasha Z, Elasasy Manar E A, El-Daly Sherien M, Mahmoud Marwa A, Awad Hanem M, Abdel Latif Nehad A

机构信息

Chemistry of Natural Compounds Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre Dokki Cairo 12622 Egypt

Applied Organic Chemistry Department, National Research Centre Dokki Cairo 12622 Egypt.

出版信息

RSC Adv. 2025 Sep 11;15(39):32821-32832. doi: 10.1039/d5ra04395f. eCollection 2025 Sep 5.

DOI:10.1039/d5ra04395f
PMID:40949040
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12423761/
Abstract

The growing evidence ascertaining the overexpression of EGFR and HDAC1 in breast and colorectal cancers prompted us to design and synthesize some new coumarin-thiazole derivatives with dual EGFR/HDAC1 inhibitory activity, considering the nature of EGFR and HDAC inhibitory models. The new derivatives were evaluated for their cytotoxicity against HCT-116 and MCF-7 cancer cells along with BJ-1 normal cells. Compound 3-(-1-((-5-(-(4-bromophenyl)diazenyl)-4-methylthiazol-2(3)-ylidene)hydrazono)ethyl)-4-hydroxy-2-chromen-2-one (3m) showed promising selectivity indices for both cell lines, preferential inhibition of EGFR/HDAC1/ERK, induction of cell cycle arrest and apoptosis, and significant antitumor activity against Ehrlich ascites and solid carcinoma models. Docking study showed that the selected compound attained promising results within the active sites of EGFR and HDAC1.

摘要

越来越多的证据证实表皮生长因子受体（EGFR）和组蛋白去乙酰化酶1（HDAC1）在乳腺癌和结直肠癌中过表达，鉴于EGFR和HDAC抑制模型的特性，促使我们设计并合成一些具有EGFR/HDAC1双重抑制活性的新型香豆素-噻唑衍生物。对这些新衍生物针对HCT-116和MCF-7癌细胞以及BJ-1正常细胞的细胞毒性进行了评估。化合物3-(-1-((-5-(-(4-溴苯基)重氮基)-4-甲基噻唑-2(3)-基亚甲基)肼基)乙基)-4-羟基-2-色原酮-2-酮（3m）对两种细胞系均显示出有前景的选择性指数、对EGFR/HDAC1/ERK的优先抑制、诱导细胞周期停滞和凋亡，以及对艾氏腹水癌和实体癌模型具有显著的抗肿瘤活性。对接研究表明，所选化合物在EGFR和HDAC1的活性位点内取得了有前景的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/9417658cd07e/d5ra04395f-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/9417658cd07e/d5ra04395f-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/84bb07af279f/d5ra04395f-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/f1bac53b68bf/d5ra04395f-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/77f71f1af1c3/d5ra04395f-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/00b0b93aefd6/d5ra04395f-f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948d/12423761/9417658cd07e/d5ra04395f-f8.jpg

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