Synthesis and biological evaluation of 3-aryl-quinolin derivatives as anti-breast cancer agents targeting ERα and VEGFR-2

Li, Xinyu; Wu, Cheng-Zhe; Lin, Xin; Cai, Xuerong; Liu, Linyi; Luo, Guoshun; You, Qidong

doi:10.1016/j.ejmech.2018.10.045

Cited by 26 publications

(7 citation statements)

References 31 publications

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“…For example, Li et al discovered some 3-aryl-quinoline derivatives 60 and 61 as dual inhibitors of both VEGFR-2 and ERα. Two molecules ( Figure 33 ) showed interesting IC 50 against ERα and VEGFR compared to the reference compounds, tamoxifen and sunitinib, respectively (for compound 60 , ERα IC 50 = 2.33 μM and VEGFR-2 IC 50 = 104 nM; for 61 , ERα IC 50 = 1.78 μM and VEGFR-2 IC 50 = 86 nM) [ 136 ].…”

Section: Quinolines As Inhibitors Of Carcinogenic Pathwaysmentioning

confidence: 99%

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

2020

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The quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized.

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Section: Quinolines As Inhibitors Of Carcinogenic Pathwaysmentioning

confidence: 99%

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

2020

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“…Cancer is one of the deadliest diseases affecting public health around the world. The occurrence and death statistics represent that it is on the rise in the developed and economically developing countries [1,2]. Cancer related deaths in females is caused primarily by breast cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Cancer related deaths in females is caused primarily by breast cancer. It constitutes 23% of the total cancer cases, out of which 14% lead to death, the incidence that rises significantly with age [1,2]. On a cellular level, cancer develops as a result of failed cell division and deregulation of signaling cascades.…”

Section: Introductionmentioning

confidence: 99%

“…Noticeably, about 30% of the primarily detected localized malignant masses will progress to an advanced or metastatic disease in 5 years [5,6]. Naphthyridine derivatives are broadly spread in naturally occurring products, principally as tricyclic benzo[f] [1,7] naphthyridines and benzo [c] naphthyridines [2,7]. These derivatives play a vital role in therapeutic products [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line

2019

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A series of new 2-phenyl-7-methyl-1,8-naphthyridine derivatives with variable substituents at C3 were synthesized for an in vitro evaluation of their anticancer activity against human breast cancer cell line (MCF7). On one hand, compounds 3f, 6f, 8c, and 10b showed IC50 values (6.53, 7.88, 7.89, 7.79 μM, respectively) compared to that of the mentioned drug staurosparine (IC50 = 4.51 μM). On the other hand, derivatives 10c, 8d, 4d, 10f and 8b displayed better activity than staurosporin with IC50 values (1.47, 1.62, 1.68, 2.30, 3.19 μM, respectively).

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“…However, the effect of M on estrogen receptor target gene sets ( Figure 2F, Figure S4E) indicates a moderate anti-estrogen effect, akin to the effect of recently developed novel quinolone derivative estrogen receptor antagonists (X. Li et al, 2019;Tang et al, 2014Tang et al, , 2016 .…”

Section: Discussionmentioning

confidence: 99%

The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

Diaz

Ahsen

Schaffter³

et al. 2019

Preprint

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Our ability to predict the effects of drug combinations is limited, in part by limited understanding of how the transcriptional response of two monotherapies results in that of their combination.We performed the first analysis of matched time course RNAseq profiling of cells treated with both single drugs and their combinations. The transcriptional signature of the synergistic combination we studied had unique gene expression not seen in either constituent monotherapy. This can be explained mechanistically by the sequential activation of transcription factors in time in the gene regulatory network. The nature of this transcriptional cascade suggests that drug synergy may ensue when the transcriptional responses elicited by two unrelated individual drugs are correlated. We used these results as the basis of a simple prediction algorithm attaining an AUROC of 0.84 in the prediction of synergistic drug combinations in an independent dataset.

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Synthesis and biological evaluation of 3-aryl-quinolin derivatives as anti-breast cancer agents targeting ERα and VEGFR-2

Cited by 26 publications

References 31 publications

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

Quinoline-Based Molecules Targeting c-Met, EGF, and VEGF Receptors and the Proteins Involved in Related Carcinogenic Pathways

Novel 1,8-Naphthyridine Derivatives: Design, Synthesis and in vitro screening of their cytotoxic activity against MCF7 cell line

The transcriptomic response of cells to a drug combination is more than the sum of the responses to the monotherapies

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