EGFR tyrosine kinase targeted compounds: synthesis, docking study, and in vitro antitumor activity of some new quinazoline and benzo[d]isothiazole derivatives

Amin, Kamelia M.; Georgey, Hanan H.; Awadallah, Fadi M.

doi:10.1007/s00044-010-9437-8

Cited by 37 publications

(8 citation statements)

References 39 publications

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“…Over‐expression of these receptors was found in many cancers such as non‐small cell lung cancer (NSCLC), breast, ovarian, colon, and prostate cancer and correlates with a poor prognosis in many cancer patients . Therefore, blocking of the kinase activity and its signal transduction pathway in cancer cells represents a rational approach to cancer therapy, and several drug discovery efforts have targeted this aberrant kinase activity in cancer . Inhibition of EGFR has been achieved through two main approaches: by blocking ligand binding to the extracellular domain with monoclonal antibodies or by using small‐molecule inhibitors that interact at the ATP‐binding site .…”

Section: Chartmentioning

confidence: 99%

4‐Substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

et al. 2014

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Four series of some 4-substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives 5a-f, 6a-f, 8a-f, and 9a-f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF-7) and lung (A-549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR-TK inhibitory activity where they revealed 41-91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP-binding site of EGFR-TK demonstrated their binding mode where H-bonding interaction with Met793 through N(1) of pyrimidine or N(2) of pyrazole was observed.

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Section: Chartmentioning

confidence: 99%

4‐Substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

et al. 2014

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“…Molecular docking became an appropriate way of the computational method in drug discovery. One of the limitations of the docking method in computational drug design is only attached a static snapshot of the ligand-protein complexes [8][9][10]. Several studies proposed to use molecular dynamics simulation (MD) in understanding the dynamic properties of the ligand-protein complex under physiological condition [11][12].…”

Section: ■ Introductionmentioning

confidence: 99%

Hydrogen Bond Stability of Quinazoline Derivatives Compounds in Complex against EGFR using Molecular Dynamics Simulation

et al. 2019

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Lung cancer was a second common cancer case due to the high cigarette smoking activity both in men and women. One of protein receptor which plays an important role in the growth of the tumor is Epidermal Growth Factor Receptor (EGFR). EGFR protein is the most frequent protein mutation in cancer and promising target to inhibit the cancer growth. In this work, the stability of the hydrogen bond as the main interaction in the inhibition mechanism of cancer will be evaluated using molecular dynamics simulation. There were two compounds (A1 and A2) as new potential inhibitors that were complexed against the EGFR protein. The dynamic properties of each complexed were compared with respect to erlotinib against EGFR. The result revealed that both compounds had an interaction in the main catalytic area of protein receptor which is at methionine residue. Inhibitor A1 showed additional interactions during simulation time but the interactions tend to be weak. Inhibitor A2 displayed a more stable interaction. Following dynamics simulation, binding free energy calculation was performed by two scoring techniques MM/GB(PB)SA method and gave a good correlation with the stability of the complex. Furthermore, potential inhibitor A2 had a lower binding free energy as a direct consequence of the stability of hydrogen bond interaction.

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“…Imidazole, a small bioactive molecule, is a prominent structural motif found in numerous biologically active compounds. Interestingly, imidazolinones such as I [12] (Figure 1) and methoxyquinazoline derivatives II , geftinib III and IV [13,14,15,16] (Figure 1) all display significant antitumor activity. Hybrid molecules combining the imidazole and quinazoline moieties in either linear or angular imidazoquinazolines were designed and demonstrated promising antitumor activity [17,18,19].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Cytotoxic Activity and 2D-QSAR Study of Some Imidazoquinazoline Derivatives

Georgey¹

2014

Molecules

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A novel series of 4-substituted amino-7,8-dimethoxy-1-phenylimidazo[1,5-a]quinazolin-5(4H)-one derivatives was designed, synthesized and tested for their antitumor activity against a human mammary carcinoma cell line (MCF7). Compound 5a was found to be the most active derivative. Physico-chemical parameters were also determined and revealed that most of the compounds obeyed the "rule of five" properties with good absorption percentages. 2D-QSAR studies revealed a well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.

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EGFR tyrosine kinase targeted compounds: synthesis, docking study, and in vitro antitumor activity of some new quinazoline and benzo[d]isothiazole derivatives

Cited by 37 publications

References 39 publications

4‐Substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

4‐Substituted‐1‐phenyl‐1H‐pyrazolo[3,4‐d]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity

Hydrogen Bond Stability of Quinazoline Derivatives Compounds in Complex against EGFR using Molecular Dynamics Simulation

Synthesis, Cytotoxic Activity and 2D-QSAR Study of Some Imidazoquinazoline Derivatives

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