Aurora kinase inhibitors as potential anticancer agents: Recent advances

Pradhan, Tathagata; Gupta, Ojasvi; Singh, Gurpreet; Monga, Vikramdeep

doi:10.1016/j.ejmech.2021.113495

Cited by 43 publications

(14 citation statements)

References 131 publications

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“…Aurora kinase is a class of serine/threonine kinase that regulates cell division. These kinases are regulatory proteins involved in centrosome maturation, chromosome alignment, chromosome segregation and cytokinesis [ 4 ]. Aurora kinase dysfunction may lead to critical, unstable chromosome content and may lead to cancer disease [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation

Elsherbeny

Ammar

Abdellattif

et al. 2022

Life

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New quinazoline derivatives were designed based on the structural modification of the reported inhibitors to enhance their selectivity toward Aurora A. The synthesized compounds were tested over Aurora A, and a cytotoxicity assay was performed over NCI cell lines to select the best candidate for further evaluation. Compound 6e (2-(3-bromophenyl)-8-fluoroquinazoline-4-carboxylic acid) was the most potent compound among the tested derivatives. A Kinase panel assay was conducted for compound 6e over 14 kinases to evaluate its selectivity profile. Further cell cycle and apoptosis analysis were evaluated for compound 6e over the MCF-7 cell line at its IC50 of 168.78 µM. It arrested the cell cycle at the G1 phase and induced apoptosis. Molecular docking was performed to explore the possible binding mode of compound 6e into the active site. It showed significant binding into the main pocket in addition to potential binding interactions with the key amino acid residues. Accordingly, compound 6e can be considered a potential lead for further structural and molecular optimization of the quinazoline-based carboxylic acid scaffold for Aurora A kinase selective inhibition with apoptosis properties.

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Section: Introductionmentioning

confidence: 99%

2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation

Elsherbeny

Ammar

Abdellattif

et al. 2022

Life

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“…AURK A and AURK B are highly expressed in dividing cells and play important roles in mitotic progression. Mammalian AURK A and AURK B share approximately 71% similarity in the carboxy-terminal catalytic domain [ 57 ]. Aberrant expression of AURK A and AURK B is involved in a broad range of solid cancers and is associated with adverse prognosis and drug resistance [ 58 , 59 ].…”

Section: Egfr-dependent Drug Resistance Mechanismsmentioning

confidence: 99%

Emerging strategies to overcome resistance to third-generation EGFR inhibitors

et al. 2022

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Epidermal growth factor receptor (EGFR), the receptor for members of the epidermal growth factor family, regulates cell proliferation and signal transduction; moreover, EGFR is related to the inhibition of tumor cell proliferation, angiogenesis, invasion, metastasis, and apoptosis. Therefore, EGFR has become an important target for the treatment of cancer, including non-small cell lung cancer, head and neck cancer, breast cancer, glioma, cervical cancer, and bladder cancer. First- to third-generation EGFR inhibitors have shown considerable efficacy and have significantly improved disease prognosis. However, most patients develop drug resistance after treatment. The challenge of overcoming intrinsic and acquired resistance in primary and recurrent cancer mediated by EGFR mutations is thus driving the search for alternative strategies in the design of new therapeutic agents. In view of resistance to third-generation inhibitors, understanding the intricate mechanisms of resistance will offer insight for the development of more advanced targeted therapies. In this review, we discuss the molecular mechanisms of resistance to third-generation EGFR inhibitors and review recent strategies for overcoming resistance, new challenges, and future development directions.

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“…Undoubtedly, it is imperative to design efficient drugs for the treatment of this disease. Based on its pathogenesis, many targets have been shown to be useful for tumor therapy, which include topoisomerase (Top) (Liang et al, 2019), aurora kinases (Pradhan et al, 2021), breast tumor kinase (Brk) (Tsui and Miller, 2015), microtubule (Kaur et al, 2014) and ras-related protein (RalA) (Fan et al, 2021), etc. Different structures of α-carboline derivatives have been designed and synthesized to regulate these targets.…”

Section: Antitumor Activitymentioning

confidence: 99%

Comprehensive review of α-carboline alkaloids: Natural products, updated synthesis, and biological activities

Yang

et al. 2022

Front. Chem.

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α-carboline (9H-pyrido[2,3-b]indole), contains a pyridine ring fused with an indole backbone, is a promising scaffold for medicinal chemistry. In recent decades, accumulating evidence shows that α-carboline natural products and their derivatives possess diverse bioactivities. However, hitherto, there is no comprehensive review to systematically summarize this important class of alkaloids. In this perspective, this paper represents the first review to provide a comprehensive description of α-carbolines including natural products, updated literature of synthesis, and their diverse biological activities. Their biological activities including antitumor, anti-microbial, anti-Alzheimer’s disease, anti-atherosclerosis, and antioxidant activities were hilighted. And the targets and the main structure activity relationships (SARs) will be presented. Finally, challenges and future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration for this group of alkaloids.

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Aurora kinase inhibitors as potential anticancer agents: Recent advances

Cited by 43 publications

References 131 publications

2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation

2-(3-Bromophenyl)-8-fluoroquinazoline-4-carboxylic Acid as a Novel and Selective Aurora A Kinase Inhibitory Lead with Apoptosis Properties: Design, Synthesis, In Vitro and In Silico Biological Evaluation

Emerging strategies to overcome resistance to third-generation EGFR inhibitors

Comprehensive review of α-carboline alkaloids: Natural products, updated synthesis, and biological activities

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