Design, Synthesis, Biological Evaluation and Docking Study of Novel Quinazoline Derivatives As EGFR-TK Inhibitors

Jin, Hao; Wu, Bai-Xu; Zheng, Qingdong; Hu, Cheng-Hai; Tang, Xiang‐Zheng; Zhang, Wen; Rao, Guo‐Wu

doi:10.4155/fmc-2020-0015

Cited by 4 publications

(3 citation statements)

References 25 publications

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“…Li and his team reported pyrimidine derivatives containing cyclopropyl moiety, which exhibited admirable kinase inhibitory activities against EGFR double mutation (L858R/T790M) with an IC 50 = 0.26 nM [ 84 ]. Similarly, Quinazoline based small molecule comprising benzazepine moiety also reduced the tumor growth with IC 50 ranging from 1.06–3.55 μM by targeting EGFR-T790M [ 85 ]. Additionally, Pyrazole moiety has been inserted in many FDA-approved drugs such as Pazopanib, which offered more potent inhibitors.…”

Section: Recent Updates On Selective Tyrosine Kinase Inhibitors In Pre-clinical Studiesmentioning

confidence: 99%

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

Mongre

Mishra

Shukla

et al. 2021

IJMS

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GLOBOCAN 2020 estimated more than 19.3 million new cases, and about 10 million patients were deceased from cancer in 2020. Clinical manifestations showed that several growth factor receptors consisting of transmembrane and cytoplasmic tyrosine kinase (TK) domains play a vital role in cancer progression. Receptor tyrosine kinases (RTKs) are crucial intermediaries of the several cellular pathways and carcinogenesis that directly affect the prognosis and survival of higher tumor grade patients. Tyrosine kinase inhibitors (TKIs) are efficacious drugs for targeted therapy of various cancers. Therefore, RTKs have become a promising therapeutic target to cure cancer. A recent report shows that TKIs are vital mediators of signal transduction and cancer cell proliferation, angiogenesis, and apoptosis. In this review, we discuss the structure and function of RTKs to explore their prime role in cancer therapy. Various TKIs have been developed to date that contribute a lot to treating several types of cancer. These TKI based anticancer drug molecules are also discussed in detail, incorporating their therapeutic efficacy, mechanism of action, and side effects. Additionally, this article focuses on TKIs which are running in the clinical trial and pre-clinical studies. Further, to gain insight into the pathophysiological mechanism of TKIs, we also reviewed the impact of RTK resistance on TKI clinical drugs along with their mechanistic acquired resistance in different cancer types.

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Section: Recent Updates On Selective Tyrosine Kinase Inhibitors In Pre-clinical Studiesmentioning

confidence: 99%

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

Mongre

Mishra

Shukla

et al. 2021

IJMS

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“…Quinazoline is an important pharmacophore as a natural product, and mainly known for its wide range of biological activities [1][2][3]. Quinazoline compounds have a variety of biological activities such as antitumor, antimalaria, anti-inflammatory, antihypertensive, antivirus and antialzheimer's disease [4][5][6][7][8]. In molecular targeted therapy, quinazoline compounds play an important role which can selectively combine with active molecules in tumor cells to treat the related diseases [9,10].…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, crystal structure and biological evaluation of novel 4-arylaminoquin- azoline derivatives as potent cytotoxic agents

Han,

Liang Chi,

Tao Qin

et al. 2023

Bull. Chem. Soc. Eth.

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ABSTRACT. A series of novel 4-arylaminoquinazoline derivatives were synthesized by five-step reactions, the structure was characterized by IR, 1H NMR, MS and single crystal X-ray diffraction. The result of 5aX crystal was as follows: the crystal belongs to the monoclinic system, space group P21/c with a = 12.3637(4) Å, b = 12.7902(2) Å, c = 13.2240(5) Å, α = 90°, β = 117.030(5)°, γ = 90°, V = 1862.75(12) Å3, Z = 2, F(000) = 804.0, µ = 0.095 mm-1, S = 1.039, R = 0.0569, wR = 0.1535 for 8417 observed reflections with I > 2σ(I). The compound 5cX exhibited an excellent inhibitory effect on the cell line A549 (IC50 ＜ 2.5 µM) and the drug-resistant cell line H1975 (IC50 ＜ 2.5 µM) by the biological activitywhich were superior to the positive control Zorifertinib (against A549: IC50 = 31.08 µM; against H1975: IC50 = 64.17 µM). Molecular docking revealed that the better inhibitory activity of compound 5cX was owing to the combining EGFRWT and EGFRL858R/T790M by hydrogen bonding. The physicochemical properties of the compounds were predicted by using ADME data analysis, and the results showed that the compounds all obeyed Lipinski's five rules. KEY WORDS: Quinazoline derivatives, Synthesis, X-ray diffraction, Antitumor activity Bull. Chem. Soc. Ethiop. 2023, 37(5), 1171-1183. DOI: https://dx.doi.org/10.4314/bcse.v37i5.10

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“…However, the adverse side effects due to the poverty of pharmacological targets remain serious problems that are difficult to overcome [ 1 , 2 ]. Besides this, the drawbacks include low water solubility, drug stability, and high efflux from cells, which constrain the therapeutic effects of drugs in tumor treatment [ 3 ]. Therefore, how to deliver drugs to the target site (tissues or cells) and release therapeutic concentrations efficiently and safely are the main challenges for innovations to chemotherapeutic agents.…”

Section: Introductionmentioning

confidence: 99%

Dual-Responsive Alginate Hydrogel Constructed by Sulfhdryl Dendrimer as an Intelligent System for Drug Delivery

Lei

Zhang

et al. 2022

Molecules

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Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.

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Design, Synthesis, Biological Evaluation and Docking Study of Novel Quinazoline Derivatives As EGFR-TK Inhibitors

Cited by 4 publications

References 25 publications

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

Design, synthesis, crystal structure and biological evaluation of novel 4-arylaminoquin- azoline derivatives as potent cytotoxic agents

Dual-Responsive Alginate Hydrogel Constructed by Sulfhdryl Dendrimer as an Intelligent System for Drug Delivery

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