Design, synthesis, and biological activity of a novel series of benzofuran derivatives against oestrogen receptor-dependent breast cancer cell lines

Jin, Liping; Xie, Qian; Huang, Er-Fang; Wang, Lin; Zhang, Bing‐Qi; Hu, Jianshu; Wan, David Chi Cheong; Jin, Zhe; Hu, Chun

doi:10.1016/j.bioorg.2020.103566

Cited by 14 publications

(11 citation statements)

References 38 publications

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“…Several compounds bearing quinoline moiety, such as Bosutinib and Anlotinib, are already being used in clinical practice to fight against cancer [36]. Similarly, a novel series of benzofuran derivatives has shown higher inhibitory effects against MDA-MB-468 human breast cancer cells [37]. The quinoline moiety has become one of the most privileged structural motifs in the discovery of anticancer agent and the present study findings are in concordance with previous studies [36].…”

Section: Discussionsupporting

confidence: 90%

Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives

et al. 2020

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Quinoline and benzofuran moieties are commonly used for the synthesis of therapeutically beneficial molecules and drugs since they possess a wide range of pharmacological activities including potent anticancer activity as compared to other heterocyclic compounds. Many of well-known antimalarial, antimicrobial, anti-helminthic, analgesic, anti-inflammatory, antiprotozoal, and antitumor compounds contain quinoline/benzofuran skeleton. The aim of this study was to analyze ten new quinoline and eighteen benzofuran derivatives for carcinoma cell line growth inhibition and to predict possible interactions with the target. The anticancer activity of these compounds against colon cancer (HCT-116) and triple-negative breast cancer (MDA-MB-468) cell lines was determined and performed molecular docking to predict the possible interactions. Among ten quinoline derivatives, Q1, Q4, Q6, Q9, and Q10 were found to be the most potent against HCT-116 and MDA-MB-468 with IC50 values ranging from 6.2-99.6 and 2.7-23.6 μM, respectively. Using the IC50 values, a model equation with quantitative structure activity relationship (QSAR) was generated with their descriptors such as HBA1, HBA2, kappa (1, 2 and 3), Balaban index, Wiener index, number of rotatable bonds, log S, log P and total polar surface area (TPSA). The effect of benzofuran derivatives was moderate in cytotoxicity tests and hence only quinolines were considered for further analysis. The molecular docking indicated the mammalian / mechanistic target of rapamycin (mTOR), Topoisomerase I and II as possible targets for these molecules. The predicted results obtained from QSAR and molecular docking analysis of quinoline derivatives showed high correlation in comparison to the results of the cytotoxic assay. Overall, this study indicated that quinolines are more potent as anticancer agents compared to benzofurans. Further, compound Q9 has emerged as a lead molecule which could be the base for further development of more potent anticancer agents.

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Section: Discussionsupporting

confidence: 90%

Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives

et al. 2020

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“…Among these compounds, 2-benzoyl-3-methyl-6-[2-(morpholin-4-yl)ethoxy] benzofuran (119) (Figure 17) owned the most potent activity against MCF-7 human breast cancer cells with inhibitory percentage of 64.23% at 50 µM and showed a low toxicity toward normal cells. Moreover, a comprehensive structure-activity relationship was extracted from this study [109].…”

Section: Benzofuran Derivativesmentioning

confidence: 99%

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

Elkaeed

Salam²,

Sabt³

et al. 2021

Molecules

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Among all cancer types, breast cancer (BC) still stands as one of the most serious diseases responsible for a large number of cancer-associated deaths among women worldwide, and diagnosed cases are increasing year by year worldwide. For a very long time, hormonal therapy, surgery, chemotherapy, and radiotherapy were used for breast cancer treatment. However, these treatment approaches are becoming progressively futile because of multidrug resistance and serious side effects. Consequently, there is a pressing demand to develop more efficient and safer agents that can fight breast cancer belligerence and inhibit cancer cell proliferation, invasion and metastasis. Currently, there is an avalanche of newly designed and synthesized molecular entities targeting multiple types of breast cancer. This review highlights several important synthesized compounds with promising anti-BC activity that are categorized according to their chemical structures.

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“…Luciferase reporter Assay confirmed that all the molecules were antagonistic towards ERα and were antiproferative in MCF-7 cells [ 233 ]. In a similar study, Jin and group used AutoDock Vina4.0 to dock Benzofuran derivatives in an attempt to identify novel SERMs using the pdb entry 3ERT as the target protein for docking [ 54 , 234 ]. The hits were tested in MCF-7 cells, MDA-MB-231 cells and HEK-293 cells giving IC 50 value comparable to that of tamoxifen and raloxifene [ 234 ].…”

Section: Small Molecule Inhibitorsmentioning

confidence: 99%

Computer-Aided Ligand Discovery for Estrogen Receptor Alpha

Bafna

Ban

Rennie

et al. 2020

IJMS

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Breast cancer (BCa) is one of the most predominantly diagnosed cancers in women. Notably, 70% of BCa diagnoses are Estrogen Receptor α positive (ERα+) making it a critical therapeutic target. With that, the two subtypes of ER, ERα and ERβ, have contrasting effects on BCa cells. While ERα promotes cancerous activities, ERβ isoform exhibits inhibitory effects on the same. ER-directed small molecule drug discovery for BCa has provided the FDA approved drugs tamoxifen, toremifene, raloxifene and fulvestrant that all bind to the estrogen binding site of the receptor. These ER-directed inhibitors are non-selective in nature and may eventually induce resistance in BCa cells as well as increase the risk of endometrial cancer development. Thus, there is an urgent need to develop novel drugs with alternative ERα targeting mechanisms that can overcome the limitations of conventional anti-ERα therapies. Several functional sites on ERα, such as Activation Function-2 (AF2), DNA binding domain (DBD), and F-domain, have been recently considered as potential targets in the context of drug research and discovery. In this review, we summarize methods of computer-aided drug design (CADD) that have been employed to analyze and explore potential targetable sites on ERα, discuss recent advancement of ERα inhibitor development, and highlight the potential opportunities and challenges of future ERα-directed drug discovery.

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Design, synthesis, and biological activity of a novel series of benzofuran derivatives against oestrogen receptor-dependent breast cancer cell lines

Cited by 14 publications

References 38 publications

Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives

Antiproliferative potential, quantitative structure-activity relationship, cheminformatic and molecular docking analysis of quinoline and benzofuran derivatives

Recent Advancements in the Development of Anti-Breast Cancer Synthetic Small Molecules

Computer-Aided Ligand Discovery for Estrogen Receptor Alpha

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