Design, synthesis, biological assessment and <i>in silico</i> ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors

Badawy, Mohamed A.; Abdelall, Eman K. A.; El‐Nahass, El‐Shaymaa; Abdellatif, Khaled R.A.; Abdel‐Rahman, Hamdy M.

doi:10.1039/d1ra04756f

Cited by 9 publications

(3 citation statements)

References 45 publications

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“…Using the PyMOL (v0.99) program, 3D interactions between ligands and proteins were clarified. [ 98 ]…”

Section: Methodsmentioning

confidence: 99%

“…In addition, evaluating other parameters, such as the calculation of topological polar surface area (TPSA) (a parameter that enables the prediction of transport properties of polar atoms through membranes), has proven useful as a virtual screening tool. [98] Herein, the physicochemical properties, pharmacokinetics, and drug-likeness profile for compound 5e were estimated using pkCSM online software pkCSM (unimelb.edu.au). (human colon adenocarcinoma) permeability coefficient model generates a tight junction between compounds' movement and transport across a monolayer.…”

Section: Absorption Distribution Metabolism Excretion and Toxicity (A...mentioning

confidence: 99%

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Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Mansour,

AboulMagd,

Abbas

et al. 2024

Archiv der Pharmazie

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Two new series of quinazoline‐chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5‐trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy‐substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)‐8226 cells by 96%, at 10 µM with IC50 = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC50 = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl‐2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI‐8226 cells showed that the trimethoxy‐substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc‐containing binding site of HDAC6 and HDAC8.

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“…Using the PyMOL (v0.99) program, 3D interactions between ligands and proteins were clarified. [ 98 ]…”

Section: Methodsmentioning

confidence: 99%

Section: Absorption Distribution Metabolism Excretion and Toxicity (A...mentioning

confidence: 99%

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Mansour,

AboulMagd,

Abbas

et al. 2024

Archiv der Pharmazie

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“…Cyclo-oxygen-ase-2 (COX-2) is widely involved in the inflammatory response and plays a crucial role in the inflammatory pathway, which can be improved by inhibiting it with NSAIDS, which can reduce the production of key pro-inflammatory mediators PG by inhibiting COX-1 and COX-2 ( 114 ). Long-term use of NSAIDS predisposes to gastrointestinal and cardiovascular diseases, which may be caused by gastric, renal, and platelet cell dysfunction due to COX-1 inhibition ( 115 ). Through research experts have found that selective COX-2 inhibitors have less side effects than non-selective COX-2 inhibitors.…”

Section: Cyclo-oxygen-ase-2 Inhibitorsmentioning

confidence: 99%

Biology of cyclooxygenase-2: An application in depression therapeutics

Han

Liao

et al. 2022

Front. Psychiatry

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Depressive Disorder is a common mood disorder or affective disorder that is dominated by depressed mood. It is characterized by a high incidence and recurrence. The onset of depression is related to genetic, biological and psychosocial factors. However, the pathogenesis is still unclear. In recent years, there has been an increasing amount of research on the inflammatory hypothesis of depression, in which cyclo-oxygen-ase 2 (COX-2), a pro-inflammatory cytokine, is closely associated with depression. A variety of chemical drugs and natural products have been found to exert therapeutic effects by modulating COX-2 levels. This paper summarizes the relationship between COX-2 and depression in terms of neuroinflammation, intestinal flora, neurotransmitters, HPA axis, mitochondrial dysfunction and hippocampal neuronal damage, which can provide a reference for further preventive control, clinical treatment and scientific research on depression.

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Novel 1,3-diaryl pyrazole derivatives bearing methylsulfonyl moiety: Design, synthesis, molecular docking and dynamics, with dual activities as anti-inflammatory and anticancer agents through selectively targeting COX-2

Shaker

Shahin

AboulMagd

et al. 2022

Bioorganic Chemistry

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Design, synthesis, biological assessment and in silico ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors

Abstract: A novel series of benzimidazole derivatives wherein 4-(methylsulfonyl) phenyl pharmacophore attached via its C-2 position was designed and synthesized.

Cited by 9 publications

References 45 publications

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Biology of cyclooxygenase-2: An application in depression therapeutics

Novel 1,3-diaryl pyrazole derivatives bearing methylsulfonyl moiety: Design, synthesis, molecular docking and dynamics, with dual activities as anti-inflammatory and anticancer agents through selectively targeting COX-2

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