Design, synthesis, and biological evaluation of pseudo-bicyclic pyrimidine-based compounds as potential EGFR inhibitors

Farag, Ahmed Karam; Ahn, Byung Sun; Yoo, Je Sik; Karam, Reham; Roh, Eun Joo

doi:10.1016/j.bioorg.2022.105918

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…The selected docking pose demonstrated that the binding energy of DHFP and EGFR tyrosine kinase was found to be −7.4 kcal/mol. Although this binding energy value is higher than that of the standard drug erlotinib which has been given as −10.6 kcal/mol [ 67 ], the DHFP does hydrogen bonds and hydrophobic interactions, as expected from an anticancer agent. The binding sites of DHFP to EGFR tyrosine kinase are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, there is no study that evaluates the anticancer effect of furo- [3,4-d] pyrimidine compounds. The closest examples are given by the two investigation of the anticancer effects of pyrimidine-based compounds on HT29 and DU145 cells [ 67 , 68 ]. It was seen that DHFP was effective at higher doses in comparison with the doses applied in these latter studies.…”

Section: Resultsmentioning

confidence: 99%

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Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Yılmaz

Uluçam

2023

Heliyon

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Yılmaz

Uluçam

2023

Heliyon

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“…In our previous literature and other reported work, [35][36][37][38][39][40][41][42][43][44][45][46] it was explored the structure and potential biological applications of bicyclic heterocycles incorporated in pyrimidine and pyridine skeletons. Building upon our prior exploration of pyridopyrimidine compounds, this review delves deeper into a specific class: pyrimido [4,5-b]quinolines, and their potential as privileged bioactive molecules.…”

Section: Introductionmentioning

confidence: 99%

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Hammouda,

Rashed,

Abo El‐Yazeed

et al. 2024

ChemistrySelect

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This study highlights the biological efficiency of pyrimido[4,5‐b]quinolines as inhibitors of cancer cell growth and antioxidants and anti‐inflammatory properties, etc. Recent research studies have revealed their promising biological activity to inhibit the growth of many disease‐causing yeasts, fungi, and bacteria. The structural composition greatly affects the biological effectiveness, as these compounds exceed the value of some standard compounds against pathogenic microbes. The antioxidant potential of these derivatives is also explored. Several glycosylated and non‐glycosylated derivatives exhibited potent free radical scavenging activity and protected against DNA damage, exceeding reference standards in some cases. Furthermore, the review examines the anti‐inflammatory and analgesic properties of pyrimidoquinoline derivatives. Studies suggest their efficacy is comparable to known drugs like diclofenac and aspirin in carrageenan‐induced paw edema and hot plate tests. Pyrimidoquinoline derivatives also demonstrate promising anticancer activity. While some have minimal effects, others exhibit notable activity against various human cancer cell lines. This review documents over two decades of research, covering the period from 2000 to 2024. Overall, pyrimidoquinoline derivatives signify an auspicious class of compounds with therapeutic potential across various areas. Further research is necessary to elucidate their mechanisms of action, optimize their efficacy and selectivity, and assess their safety profiles for clinical development.

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“…Contrary to normal cells with tightly controlled EGFR pathways, tumour cells exhibit dysregulated EGFR signalling due to receptor overexpression and/or mutation 9 . This causes angiogenesis to rise and proliferation under unfavourable conditions, leading to the development of many cancers, such as NSC lung cancer 10 , breast cancer 11 , prostate cancer 12 , and colon cancer 13 . EGFR is a valid therapeutic target as a result 14 .…”

Section: Introductionmentioning

confidence: 99%

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR ^WT , EGFR ^T790M , and EGFR ^L858R )

Abo Al-Hamd,

Tawfik,

Abdullah

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for 10c . Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFR WT , EGFR T790M , and EGFR L858R where compound 10d was the best inhibitor with IC 50 = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC 50 = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. 10c and 10d disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.

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Design, synthesis, and biological evaluation of pseudo-bicyclic pyrimidine-based compounds as potential EGFR inhibitors

Cited by 5 publications

References 35 publications

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR ^WT , EGFR ^T790M , and EGFR ^L858R )

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Design, synthesis, and biological evaluation of pseudo-bicyclic pyrimidine-based compounds as potential EGFR inhibitors

Cited by 5 publications

References 35 publications

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Novel N-benzyl-2-oxo-1,2-dihydrofuro [3,4-d]pyrimidine-3(4H)-carboxamide as anticancer agent: Synthesis, drug-likeness, ADMET profile, DFT and molecular modelling against EGFR target

Recent Advancements and Developments in the Biological Importance of Pyrimido[4,5‐b]Quinoline Scaffolds

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR WT , EGFR T790M , and EGFR L858R )

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Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR ^WT , EGFR ^T790M , and EGFR ^L858R )