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, Ahmed; Shahin, Mai I.; AboulMagd, Asmaa M.; Aleem, Seham A. Abdel; Abdel‐Rahman, Hamdy M.; Ella, Dalal A. Abou El

doi:10.1016/j.bioorg.2022.106143

Cited by 14 publications

(11 citation statements)

References 55 publications

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“…Though the literature evidence the design, synthesis, and potent anti‐inflammatory activity of several pyrazole analogs, still, there is a need for the development of an anti‐inflammatory drug containing this scaffold with low side effects and less or no toxicity compared to the available drug celecoxib [143–146] …”

Section: Small Molecules As Potent Anti‐inflammatory Agentsmentioning

confidence: 99%

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

Basha¹

2023

ChemistrySelect

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Cancer and inflammation interlink with many pathways. Millions of people died because of these two disorders. Major pathways that cause both inflammation and cancer are STAT3, NF‐κB, COX, and histone acetylation. However, these are the target for medicinally potent heterocycles such as pyrimidines, indole, and pyrazole. Many NSAIDs reported in the literature belong to both natural and synthetic molecules. This review encompasses molecular mechanisms for inflammation, NSAIDs derived from natural sources and synthetic methods, and recent reports on heterocycles as potent anti‐inflammatory agents and their significance in cancer treatment. Literature for the study, accomplished from 2019 to 2022.

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Section: Small Molecules As Potent Anti‐inflammatory Agentsmentioning

confidence: 99%

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

Basha¹

2023

ChemistrySelect

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“…carcinoma colon cancer (HCT-116), and mammary gland breast cancer (MCF-7) cell lines from ATCC. 49 The aforementioned cell lines were used to examine the drug's inhibitory effects on cell growth using the MTT assay. In RPMI-1640 media with 10% foetal bovine serum, cell lines were grown.…”

Section: Chemistrymentioning

confidence: 99%

“…The cell lines were seeded at a density of 1.0 × 10 4 cells per well in a 96-well plate and incubated for 48 h at 37 °C with 5% CO 2 . 49 4.2.2. Enzyme inhibition activity.…”

Section: Chemistrymentioning

confidence: 99%

“…This test protocol was followed as specied by the manufacturer. 49 In vitro enzyme test for cyclin-dependent kinase/cyclin 2A inhibition. The ADP-GloTM Kinase assay methodology was used for the CDK2/Cyclin2A enzyme inhibition assay.…”

Section: Chemistrymentioning

confidence: 99%

“…A combination of Discovery Studio Client Visualizer 2021 and Pymol 2.5 was used to generate 2D and 3D captions. 49,62,63…”

Section: Molecular Docking Studymentioning

confidence: 99%

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Pyrrolizine/indolizine-bearing (un)substituted isoindole moiety: design, synthesis, antiproliferative and MDR reversal activities, and in silico studies

AbdelSamad,

El-Saadi,

Gouda

et al. 2023

RSC Adv.

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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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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

Cited by 14 publications

References 55 publications

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

Pyrrolizine/indolizine-bearing (un)substituted isoindole moiety: design, synthesis, antiproliferative and MDR reversal activities, and in silico studies

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

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