Eco-friendly and regiospecific intramolecular cyclization reactions of cyano and carbonyl groups in N,N-disubstituted cyanamide

Moustafa, Amr H.; Ahmed, Walaa W.; Awad, Mohamed F.; Aboelez, Moustafa O.; Khodairy, A.; Amer, Amer A.

doi:10.1007/s11030-022-10401-z

Cited by 16 publications

(12 citation statements)

References 34 publications

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“…Docking studies were performed for the compounds 15–21 against the ATP binding sites of EGFR-TK Wild-type (EGFR WT , PDB:4HJO) 47 and EGFR-TK mutant type (EGFR T790M , PDB: 3W2O). 48 , 49 The docked compounds revealed good binding affinities against EGFR WT (energy score −7.50 to − 8.65 kcal mol −1 ; Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M

Aboelez

Belal

Xiang

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new class of EGFR PROTACs based on pomalidomide was developed, synthesised, and tested for their cytotoxic activity against a panel of human cancer cells. Compounds 15 – 21 were showed to be more effective against the four tested cell lines than erlotinib. In particular, compound 16 was found to be the most potent counterpart as it was 5.55, 4.34, 5.04, and 7.18 times more active than erlotinib against MCF-7, HepG-2, HCT-116, and A549 cells, respectively. Compound 15 was revealed to be more active than doxorubicin against the four tested cell lines. Furthermore, the most potent cytotoxic compounds were studied further for their kinase inhibitory effects against EGFR WT and EGFR T790M using HTRF test. Compound 16 showed to be the most effective against both kinds of EGFR, with IC 50 values of 0.10 and 4.02 µM, respectively. Compound 16 could effectively degrade EGFR protein through ubiquitination (D max = 96%) at 72 h in the tested cells.

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Section: Resultsmentioning

confidence: 99%

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M

Aboelez

Belal

Xiang

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Then, the ligand pharmacophore mapping protocol was used in the virtual screening process. The most predictive model was used as 3D queries to identify compounds with high fit values [ 36 , 37 , 38 , 39 ].…”

Section: Methodsmentioning

confidence: 99%

Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management

et al. 2022

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Keratoconus (KC) is a serious disease that can affect people of any race or nationality, although the exact etiology and pathogenic mechanism are still unknown. In this study, thirty-two FDA-approved ophthalmic drugs were exposed to virtual screening using docking studies against both the MMP-2 and MMP-9 proteins to find the most promising inhibitors as a proposed computational mechanism to treat keratoconus. Matrix metalloproteinases (MMPs) are zinc-dependent proteases, and MMP inhibitors (MMPIs) are usually designed to interact with zinc ion in the catalytic (CAT) domain, thus interfering with enzymatic activity. In our research work, the FDA-approved ophthalmic medications will be investigated as MMPIs, to explore if they can be repurposed for KC treatment. The obtained findings of the docking study suggest that atenolol and ampicillin are able to accommodate into the active sites of MMP-2 and MMP-9. Additionally, both exhibited binding modes similar to inhibitors used as references, with an ability to bind to the zinc of the CAT. Molecular dynamic simulations and the MM-GBSA binding free-energy calculations revealed their stable binding over the course of 50 ns. An additional pharmacophoric study was carried out on MMP-9 (PDB ID: 1GKC) using the co-crystallized ligand as a reference for the future design and screening of the MMP-9 inhibitors. These promising results open the door to further biological research to confirm such theoretical results.

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“…[14,15] Further pyrimidine-5-carbonitrile derivatives (Series III) were introduced as anticancer agents targeting EGFR WT and EGFR T790M (Figure 2). [16,17] Despite the potent activity of available anti-EGFR agents, a new mutant epidermal growth factor receptor (EGFR) has been discovered with acquired drug resistance. [18] Fortunately, several studies documented tri-substituted imidazoles as inhibitors of the drug-resistant EGFR(L858R/T790M/C797S).…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activities of Tetrasubstituted Imidazole‐Pyrimidine‐Sulfonamide Hybrids as Inhibitors of EGFR Mutants

et al. 2023

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A new series of tetrasubstituted imidazole derivatives carrying pyrimidine sulfonamide pharmacophores has been synthesized and evaluated for their anticancer activities. In‐vitro screening of these hybrids against a full 60‐cell‐line panel at a single dose of 10 μM showed significant growth inhibition of up to 95 %. The most active compound showed in‐vitro anticancer activities against (i) abnormal HER2 and (ii) two mutants for EGFR. Apoptotic gene expression revealed that lead compounds induced MCF‐7 cell line apoptosis together with considerable change in the Bax/Bcl‐2 expression ratio. One lead compound led to a significant cell‐cycle S‐phase arrest, while another blocked the cell cycle at G1/S‐phase causing the accumulation of cells. Docking analysis of these two hybrids adopted the orientation and binding interactions with a higher liability to enter the active side pocket of HER2, L858R, and T790 M, preferable to that of co‐crystallized ligands. Modelling simulation was consistent with the acquired biological evaluation.

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Eco-friendly and regiospecific intramolecular cyclization reactions of cyano and carbonyl groups in N,N-disubstituted cyanamide

Cited by 16 publications

References 34 publications

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M

Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management

Anticancer Activities of Tetrasubstituted Imidazole‐Pyrimidine‐Sulfonamide Hybrids as Inhibitors of EGFR Mutants

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Eco-friendly and regiospecific intramolecular cyclization reactions of cyano and carbonyl groups in N,N-disubstituted cyanamide

Cited by 16 publications

References 34 publications

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFRWT and EGFRT790M

Screening a Panel of Topical Ophthalmic Medications against MMP-2 and MMP-9 to Investigate Their Potential in Keratoconus Management

Anticancer Activities of Tetrasubstituted Imidazole‐Pyrimidine‐Sulfonamide Hybrids as Inhibitors of EGFR Mutants

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Product

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Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M

Design, synthesis, and molecular docking studies of novel pomalidomide-based PROTACs as potential anti-cancer agents targeting EGFR^WT and EGFR^T790M