Pyrimidine-based EGFR TK inhibitors in targeted cancer therapy

Ayati, Adileh; Moghimi, Setareh; Toolabi, Mahsa; Foroumadi, Alireza

doi:10.1016/j.ejmech.2021.113523

Cited by 58 publications

(47 citation statements)

References 89 publications

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“…EGFR is a receptor binding the extracellular epidermal growth factor family (EGF family) [156]. In many tumor types, including TC, increased EGFR expression or activity initiates the tumor cell progression [112].…”

Section: Egfr-targeting Probesmentioning

confidence: 99%

Next-Generation Molecular Imaging of Thyroid Cancer

Jin

Liu

Younis

et al. 2021

Cancers

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An essential aspect of thyroid cancer (TC) management is personalized and precision medicine. Functional imaging of TC with radioiodine and [18F]FDG has been frequently used in disease evaluation for several decades now. Recently, advances in molecular imaging have led to the development of novel tracers based on aptamer, peptide, antibody, nanobody, antibody fragment, and nanoparticle platforms. The emerging targets—including HER2, CD54, SHP2, CD33, and more—are promising targets for clinical translation soon. The significance of these tracers may be realized by outlining the way they support the management of TC. The provided examples focus on where preclinical investigations can be translated. Furthermore, advances in the molecular imaging of TC may inspire the development of novel therapeutic or theranostic tracers. In this review, we summarize TC-targeting probes which include transporter-based and immuno-based imaging moieties. We summarize the most recent evidence in this field and outline how these emerging strategies may potentially optimize clinical practice.

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Section: Egfr-targeting Probesmentioning

confidence: 99%

Next-Generation Molecular Imaging of Thyroid Cancer

Jin

Liu

Younis

et al. 2021

Cancers

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“…Finally, twenty-six targeted furfuryl or benzyl 2-(substituted arylmethyl)-1-oxo-1,2,3,4-tetrahydropyrazino [1,2-a]indole-3-carboxamide analogs (1a-m and 2a-m) were prepared by direct transamidation from methyl esters (7a-m) with furfurylamine and benzylamine, respectively, in 28-88% yield. All target compounds were identified by 1 H NMR, 13 C NMR, and HRMS (see Supplementary Materials).…”

Section: Preparation Of Pyrazino[12-a]indole-3-carboxamide Analogsmentioning

confidence: 99%

“…Chemical shifts were reported in ppm from tetramethylsilane (TMS) with the solvent resonance resulting from incomplete deuteration as the internal reference (CDCl 3 : 7.26 ppm) or relative to TMS (δ = 0.0). 13 C NMR spectra were recorded on a JEOL JNM-EX400 (100 MHz) with complete proton decoupling. Chemical shifts were reported in ppm from tetramethylsilane with the solvent as the internal reference (CDCl 3 : 77.16 ppm).…”

Section: Chemistrymentioning

confidence: 99%

“…The following are available online at https://www.mdpi.com/article/10 .3390/ph14100974/s1, Figures S1-S39: 1 H and 13 C NMR specta of componds 7a-m, 2a-m, and 1a-m.…”

Section: Supplementary Materialsmentioning

confidence: 99%

“…In targeted therapy against lung cancer, many studies have focused on the more common non-small cell lung cancer (NSCLC) and involve inhibitors related to the epidermal growth factor receptor (EGFR) pathway, including the PI3K/AKT/mTOR and RAS-MAPK pathways, anaplastic lymphoma kinase (ALK), proto-oncogene ROS1, and programmed death 1 (PD-1) [7][8][9][10][11]. Among them, the EGFR pathway is considered an attractive target; thus, anti-EGFR therapies such as epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors and monoclonal antibodies have been developed [12,13]. Targeted therapy against breast cancer involves the overexpression of specific receptors and their downstream signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and Biological Evaluation of (S)-2-(Substituted arylmethyl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide Analogs and Their Synergistic Effect against PTEN-Deficient MDA-MB-468 Cells

et al. 2021

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A series of twenty-six compounds of furfuryl or benzyl tetrahydropyrazino[1,2-a]indole analogs were synthesized and evaluated for cytotoxic activity against the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) and the epidermal growth factor receptor (EGFR) over-expressed triple-negative breast cancer cell line (MDA-MB-468). Among them, compounds 2b, 2f and 2i showed more potent activity and selectivity against MDA-MB-468 cells than gefitinib, as an EGFR- tyrosine kinase inhibitor. In addition, it was confirmed by means of isobologram analysis of combinational treatment with gefitinib that they have a synergistic effect, especially compounds 2b and 2f, which inhibit Akt T308 phosphorylation. Moreover, it was confirmed that 2-benzyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide analogs (2b, 2f, and Ref2) tend to selectively inhibit PI3Kβ, which is involved in the phosphorylation of Akt.

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Self‐assembled neutral and ionic [2 + 2] metallomacrocycles using a new flexible ditopic Pt(II)‐based organometallic tecton bearing a pyrimidine motif: Facile syntheses and enhanced anticancer potency

Chakraborty

Pandey

et al. 2022

Applied Organom Chemis

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A new di‐platinum(II) organometallic compound (3) has been synthesized from a readily available pyrimidine derivative in two steps. 3 is a conformationally flexible molecule due to the presence of ethereal linkages. The application of 3 as an acceptor tecton in supramolecular chemistry was explored using coordination‐driven self‐assembly protocol. Thus, three neutral (M1–M3) and two ionic (M4 and M5) metallomacrocycles were obtained in high yields, the structures of which included biologically active pyrimidine and π‐conjugated trans‐Pt(II)‐alkynyl motifs. Formation of these five flexible [2 + 2] ensembles (M1–M5) was confirmed using FT‐IR and NMR spectroscopy (1H, 31P{1H}, 13C{1H}, and 1H DOSY) as well as HRMS experiments. DFT calculations suggest that the macrocycles have nano‐scalar dimensions with well‐defined cavities. Cytotoxicity of 3 and macrocycles (M1–M5) were estimated against A549 human lung cancer cell line. Results indicate improvement in cytotoxicity upon self‐assembly of 3 with neutral and ionic donor tectons to yield, respectively ionic and neutral macrocycles (M1–M5). Although the organometallic molecule 3 is almost seven times more potent than cisplatin, the antiproliferative potencies of the macrocycles (M1–M5) are up to 17 times better than cisplatin. Annexin V‐FITC assay studies show that post‐treatment with the organometallic 3, or the macrocycles (M1–M5), the A549 cancer cells are present in the early apoptosis stage.

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Pyrimidine-based EGFR TK inhibitors in targeted cancer therapy

Cited by 58 publications

References 89 publications

Next-Generation Molecular Imaging of Thyroid Cancer

Next-Generation Molecular Imaging of Thyroid Cancer

Synthesis and Biological Evaluation of (S)-2-(Substituted arylmethyl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide Analogs and Their Synergistic Effect against PTEN-Deficient MDA-MB-468 Cells

Self‐assembled neutral and ionic [2 + 2] metallomacrocycles using a new flexible ditopic Pt(II)‐based organometallic tecton bearing a pyrimidine motif: Facile syntheses and enhanced anticancer potency

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