Synthesis and structure–activity relationships of novel hybrid ferrocenyl compounds based on a bicyclic core skeleton for breast cancer therapy

Li, Changhao; Tang, Chu; Hu, Zhigang; Zhao, Chenxi; Li, Chenlu; Zhang, Silong; Dong, Chune; Zhou, Hai-Bing; Huang, Jian

doi:10.1016/j.bmc.2016.05.019

Cited by 23 publications

(10 citation statements)

References 46 publications

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“…As shown in Table 3 , DS 2D descriptors without ECFP_6 were also not better than MOE 2D descriptors in test set, which maybe DS 2D descriptors did not characterize the important substructures and molecular fragments which are critical for ER α antagonist. Then, compounds in external test set, which were not involved in the training and test set, were extracted from literatures published in recent years for further validation [ 6 , 43 – 46 ]. The external test set included 20 antagonists and 50 inactive compounds.…”

Section: Resultsmentioning

confidence: 99%

Identification of Estrogen Receptor α Antagonists from Natural Products via In Vitro and In Silico Approaches

Pang

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

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Estrogen receptor α (ERα) is a successful target for ER-positive breast cancer and also reported to be relevant in many other diseases. Selective estrogen receptor modulators (SERMs) make a good therapeutic effect in clinic. Because of the drug resistance and side effects of current SERMs, the discovery of new SERMs is given more and more attention. Virtual screening is a validated method to high effectively to identify novel bioactive small molecules. Ligand-based machine learning methods and structure-based molecular docking were first performed for identification of ERα antagonist from in-house natural product library. Naive Bayesian and recursive partitioning models with two kinds of descriptors were built and validated based on training set, test set, and external test set and then were utilized for distinction of active and inactive compounds. Totally, 162 compounds were predicted as ER antagonists and were further evaluated by molecular docking. According to docking score, we selected 8 representative compounds for both ERα competitor assay and luciferase reporter gene assay. Genistein, daidzein, phloretin, ellagic acid, ursolic acid, (−)-epigallocatechin-3-gallate, kaempferol, and naringenin exhibited different levels for antagonistic activity against ERα. These studies validated the feasibility of machine learning methods for predicting bioactivities of ligands and provided better insight into the natural products acting as estrogen receptor modulator, which are important lead compounds for future new drug design.

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Section: Resultsmentioning

confidence: 99%

Identification of Estrogen Receptor α Antagonists from Natural Products via In Vitro and In Silico Approaches

Pang

Wang

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…In recent research, a series of dual-acting ER and HDAC inhibitors were designed with incorporation of a ferrocenyl moiety, leading to novel hybrid ferrocenyl conjugates (FcOBHS-HDAC inhibitors) against breast cancer. These ferrocenyl conjugates can inhibit both the proliferation of ERα-positive (MCF-7) and ER-negative breast cancer cells (MDA-MB-231), and are a very promising strategy against breast cancer (122).…”

Section: N-(2-hydroxyphenyl)-2propylpentanamide N-(2-hydroxy-mentioning

confidence: 99%

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

et al. 2017

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Abstract. With a lifetime risk estimated to be one in eight in industrialized countriesBreast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among women worldwide. According to the American Cancer Society about 12% U.S. women will develop breast cancer during their lifetime. Moreover, in 2015, about 2,300 men were diagnosed with breast cancer and 440 died from the disease (1, 2).In approximately 90% of breast cancer cases, estrogen receptor α (ERα), progesterone receptor (PR), or the human epidermal growth factor receptor2 (HER2/ERBB2) protooncogenic receptor are expressed. In many of these patients, treatment with anti-estrogens (e.g. aromatase inhibitors, tamoxifen, fulvestrant) and HER2-targeted agents has improved their survival significantly (3, 4). However, despite 35

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“…The flexibility in noncatalytic structural domains provides scope for easy tuning of HDACis with other pharmacophore elements to generate a 'hybrid HDACi' that represents multiple therapeutic activities (168). Several of these have been reported to be potential therapeutics against breast cancer treatment as well (169)(170)(171). These initiatives promote the much-needed addition of novel therapeutics to the pipeline against breast cancers, as no present strategies are efficient in treatment of TNBC, and no HDACi have yet been approved by the FDA either.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment

Mody

Bouckaert

Savvides

et al. 2021

CPD

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Background: Breast cancer is the most prevalent cancer amongst females across the globe and with over 2 million new cases reported in 2018, it poses huge economic burden to the already dwindling public health. A dearth of therapies in the pipeline to treat triple-negative breast cancers, and acquisition of resistance against existing line of treatments urges the need to strategize novel therapeutics in order to add new drugs to the pipeline. HDAC inhibitors (HDACi) is one such class of small molecule inhibitors that target histone deacetylases to bring about chromosomal remodelling and normalize dysregulated gene expression that marks breast cancer progression. Objective: While four HDACi have been approved by the FDA for treatment of different cancer types, no HDACi is specifically earmarked for clinical management of breast cancer. Owing to the differential HDAC expression pertaining to different types of breast cancers, isoform-selective HDAC inhibitors need to be discovered. Conclusion: This review attempts to set the stage for rational structure-based discovery of isoform-selective HDACi by providing structural insights into different HDACs and their catalytic folds based on their classes and individual landscape. Development of inhibitors in accordance with the differential expression of HDAC isoforms exhibited in breast cancer cells is a promising strategy to rationally design selective and effective inhibitors, adopting a ‘personalized-medicine’ approach.

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Synthesis and structure–activity relationships of novel hybrid ferrocenyl compounds based on a bicyclic core skeleton for breast cancer therapy

Cited by 23 publications

References 46 publications

Identification of Estrogen Receptor α Antagonists from Natural Products via In Vitro and In Silico Approaches

Identification of Estrogen Receptor α Antagonists from Natural Products via In Vitro and In Silico Approaches

Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer

Rational Design and Development of HDAC Inhibitors for Breast Cancer Treatment

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