Targeting EGFR, RSK1, RAF1, PARP2 and LIN28B for several cancer type therapies with newly synthesized pyrazole derivatives via a computational study

Bennani, Fatima Ezzahra; Doudach, Latifa; Karrouchi, Khalid; Tarib, Abdelilah; Rudd, Christopher E.; Ansar, Mʼhammed; Faouzi, My El Abbés

doi:10.1080/07391102.2022.2064915

Cited by 5 publications

(1 citation statement)

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“…Based on the above facts and in continuation of our research on the identification and development of new anticancer agents, [15][16][17][18][19] Herein we report the design and synthesis of novel hybrid compounds between pyrazole and benzofuran assembled by a hydrazone moiety.…”

Section: Introductionmentioning

confidence: 99%

Novel Pyrazole‐Based Benzofuran Derivatives as Anticancer Agents: Synthesis, Biological Evaluation, and Molecular Docking Investigations

Ameziane El Hassani,

Altay,

Karrouchi

et al. 2023

Chemistry & Biodiversity

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In this work, the design, synthesis and mechanistic studies of a novel pyrazole‐based benzofuran derivatives 1‐8 as anticancer agents were discussed. Cytotoxic potency of the title compounds was evaluated against the lung carcinoma A‐549, human‐derived colorectal adenocarcinoma HT‐29, breast adenocarcinoma MCF‐7 cells as well as mouse fibroblast 3T3‐L1 cells using XTT assay. Anticancer mechanistic studies were carried out with flow cytometry. XTT results revealed that all compounds exhibited dose‐dependent anti‐proliferative activity against the tested cancer cells, and especially compound 2 showed the strongest anti‐proliferative activity with an IC50 value of 7.31 µM and the highest selectivity (15.74) on MCF‐7 cells. Flow cytometry results confirmed that the cytotoxic power of the compound 2 on MCF‐7 cells is closely related to the mitochondrial membrane damage, caspase activation, and apoptosis orientation. Finally, molecular docking studies were applied to determine the interactions between compound 2 and caspase‐3 via in‐silico approaches. By molecular docking studies, free binding energy (ΔGBind), docking score, Glide score values as well as amino acid residues in the active binding site were determined. Consequently, these results constitute a preliminary data for in vivo anticancer studies and have the potential as a chemotherapeutic agent.

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