Indole: A privileged scaffold for the design of anti-cancer agents

Wan, Yicong; Li, Yuanhua; Yan, Chunxing; Mi, Yan; Tang, Zilong

doi:10.1016/j.ejmech.2019.111691

Cited by 345 publications

(176 citation statements)

References 110 publications

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“…Indoles are the most abundant heterocycles in biologically active natural products and synthetic Nheterocycles, which are also considered as the privileged structures existing in pharmaceuticals, agrochemicals and advanced functional materials. [10] Due to the important applications of indole scaffolds, various synthetic methods have been developed to access indole moieties, including the typical improved Fischer indole synthesis, intramolecular cycloaddition of anilines to alkynes, metal-catalyzed cascade reactions and transition-metal-catalyzed CÀ H activation reactions. [11] Among all the existing synthetic methods, the classical Fischer indole synthesis is also constantly improved and remains attractive in medicinal chemistry and natural products synthesis due to its simplicity and reliability.…”

Section: Synthesis Of Indolesmentioning

confidence: 99%

Recent Advances in the Synthesis of Nitrogen Heterocycles Using Arenediazonium Salts as Nitrogen Sources

et al. 2020

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Nitrogen heterocycles are important structural subunits that occur widely in bioactive natural products, pharmaceuticals, agrochemicals, dyes, cosmetics, and functional materials. Considering the importance of these useful compounds in modern science, the synthesis of N-heterocycles and their derivatives has always been a hot topic in organic synthesis. Recently, arenediazonium salts which can be easily prepared from inexpensive and abundantly available anilines, have been used as versatile nitrogen sources in the field of nitrogen heterocycle synthetic chemistry due to their ready availability, rich reactivity, and diverse transformations. The aim of the present review is to summarize the recent advances in the synthesis of nitrogen heterocycles using arenediazonium salts as nitrogen sources in the past ten years. Hopefully, it can provide practical guidance for the readers who are interested in utilizing arenediazonium salts as building blocks in organic synthesis. For simplicity and clarity, the organization of this review is based on the number of N atoms in the ring of nitrogen heterocycle.

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Section: Synthesis Of Indolesmentioning

confidence: 99%

Recent Advances in the Synthesis of Nitrogen Heterocycles Using Arenediazonium Salts as Nitrogen Sources

et al. 2020

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“…Indoles are bicyclic heterocycles that are commonly found in plants, bacteria and animals. Natural and synthetic indole-based compounds have widely been used as antibacterial, antifungal, anti-inflammatory, antihistaminic and anticancer drugs [ 27 , 28 ]. Examples of such compounds currently in clinical use are the non-steroidal anti-inflammatory drug indomethacin [ 29 ] or the antiretroviral delavirdine [ 30 ].…”

Section: Introductionmentioning

confidence: 99%

“…Examples of such compounds currently in clinical use are the non-steroidal anti-inflammatory drug indomethacin [ 29 ] or the antiretroviral delavirdine [ 30 ]. On the anticancer front, numerous indole-based compounds have been developed to interfere with tubulin formation (necessary for cellular division) [ 31 ], inhibit histone deacilase [ 32 , 33 ] or sirtuins [ 34 ] (involved in gene expression), hamper DNA topoisomerase (involved in DNA transcription) or affect DNA directly via formation of inter- and intra-strand cross links [ 27 , 28 ]. Some notable examples are vincristine, a known antimitotic agent used for the treatment of some cancers [ 35 , 36 ], and mitomycin C, which undergoes in vivo reductive activation to form cross-links with DNA [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterisation and In Vitro Anticancer Activity of Catalytically Active Indole-Based Half-Sandwich Complexes

et al. 2020

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The synthesis, characterisation and evaluation of the in vitro cytotoxicity of four indole-based half-sandwich metal complexes towards two ovarian cancer cell lines (A2780 and A2780cisR) and one normal prostate cell line (PNT2) are presented herein. Although capable of inducing catalytic oxidation of NADH and able to reduce NAD+ with high turnover frequencies, in cells and in the presence of sodium formate, these complexes also strongly interact with biomolecules such as glutathione. This work highlights that efficient out-of-cells catalytic activity might lead to higher reactivity towards biomolecules, thus inhibiting the in-cells catalytic processes.

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“…MCL-1 encodes an anti-apoptotic protein that is an important member of the Bcl-2 family [8]. Multiple transcript variants can be produced as a result of alternative splicing, and they have many anti-apoptotic roles [9,10]. MCL-1 protein localizes in the outer mitochondrial membrane, sequestering Bak and preventing the release of cytochrome c [11,12].…”

Section: Introductionmentioning

confidence: 99%

MCL-1 plays an oncogenic role in breast cancer by modulating chemoresistance and stemness properties by activating Wnt/β-catenin

Zhang

Zhu

Zhang

et al. 2020

Preprint

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Background Breast cancer is the most common malignant tumor and the leading cause of death in women. Chemotherapy is one of the most important treatments for breast cancer. However, the development of chemotherapy resistance is the main cause of 20–30% of breast cancer patients developing metastasis, leading to death. MCL-1, an anti-apoptotic protein, has not been found to contribute to chemotherapy resistance in breast cancer. Methods We used large gene panels to detect pathological sections of tumors in drug-resistant and sensitive patients. We validated protein profiling by IHC in a larger cohort of samples. We performed the function of MCL-1 by knockdown and overexpression in vitro and in vivo. Luciferase assay and CHIP assay were used to prove the regulatory network between MCL-1 and LRP6. Result We found that MCL-1 is more highly expressed in drug-resistant breast cancer tissues than it is in sensitive breast cancer tissues. Functional studies have revealed that MCL-1 plays an important role in drug resistance by regulating apoptosis in breast cancer cells. We found that overexpression of MCL-1 enhances the chemoresistance and stemness of breast cancer cells in vitro and in vivo, while silencing has the opposite effect. Mechanistically, by downregulating and upregulating MCL-1, we show that MCL-1 regulates LRP6 and activates the WNT/β-catenin signaling pathway in breast cancer cells. Finally, we found that a high level of MCL-1 expression predicts a poor prognosis in breast cancer. Conclusion Our work highlights the role of MCL-1 in chemoresistance and stemness. The MCL-1-WNT/β-catenin axis might be used as a new clinical target for breast cancer therapy.

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Indole: A privileged scaffold for the design of anti-cancer agents

Cited by 345 publications

References 110 publications

Recent Advances in the Synthesis of Nitrogen Heterocycles Using Arenediazonium Salts as Nitrogen Sources

Recent Advances in the Synthesis of Nitrogen Heterocycles Using Arenediazonium Salts as Nitrogen Sources

Synthesis, Characterisation and In Vitro Anticancer Activity of Catalytically Active Indole-Based Half-Sandwich Complexes

MCL-1 plays an oncogenic role in breast cancer by modulating chemoresistance and stemness properties by activating Wnt/β-catenin

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