Quinoline‐based thiazolidinone derivatives as potent cytotoxic and apoptosis‐inducing agents through EGFR inhibition

Abstract

Quinoline-based thiazolidinone heterocycles exhibited potent activity in the field of cancer therapy. Hence, ten quinoline-based thiazolidinone derivatives were evaluated for their anticancer activity through cytotoxic activity, epidermal growth factor receptor (EGFR) inhibition pathway, apoptosis investigation through flow cytometric analyses, RT-PCR gene expression, in vivo solid-Ehrlich carcinoma model, and finally in silico approach for highlighting the interaction pose. Results revealed that compound 7 exhibited cytotoxic activity against HCT-116 cells with an IC 50 value of 7.43 µM compared to 5-FU (IC 50 = 11.36 µM) with moderate cytotoxic activity against the FHC (IC 50 = 35.27 µM), and it exhibited remarkable inhibition activity of EGFR with IC 50 value of 96.43 nM compared to Erlotinib (IC 50 = 78.65 nM). Moreover, it significantly stimulated apoptotic colon cancer cell death with 171.58-fold arresting cell cycle at G2 and S-phases.Additionally, it ameliorated both biochemical and histochemical structures near normal with tumor inhibition ratio of 52.92% compared to 5-FU of 57.16%, with immunohistochemical examinations of EGFR inhibition in the treated group compared to control. Finally, molecular docking study highlighted its good binding affinity through good interactive binding pose inside the EGFR protein. In conclusion, the potent EGFR inhibitory activity of compound 7 was investigated using three integrated approaches in vitro, in vivo, and in silico, so it worth be validated and developed as a chemotherapeutic anticancer agent.

Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent

“…As cyclic-dependent kinase (CDK-2) and epidermal growth factor receptor (EGFR) are key proteins that mediate and trigger the proliferation of cancer cells, their inhibition is an interesting target for apoptosis induction upon treatment of a chemotherapeutic drug. − A molecular docking study was performed to highlight the virtual mechanism of binding toward EGFR and CDK-2 proteins. As seen in Figure , compound 3b was docked inside the EGFR binding site with the binding energy of −19.63 kcal/mol, and it formed one H-bind interaction with Met 769 as the H-bond acceptor.…”

Quinoline–hydrazone hybrids as dual mutant EGFR inhibitors with promising metallic nanoparticle loading: rationalized design, synthesis, biological investigation and computational studies

“…The percentage inhibition of autophosphorylation by substances was estimated using the following equation: . 107,108…”

Rational Design, Synthesis and Biological Evaluation of Novel Pyrazoline-Based Antiproliferative Agents in MCF-7 Cancer Cells

“…The cells were suspended in 100 µL of annexin-binding buffer solution “25 mM CaCl 2 , 1.4 M NaCl, and 0.1 M Hepes/NaOH, pH 7.4” and incubated with “Annexin V-FITC solution (1:100) and propidium iodide (PI)” at a concentration equal 10 µg/mL in the dark for 30 min. Stained cells were then obtained by a Cytoflex FACS machine, and data analysis was performed using cytExpert software [ 71 , 72 , 73 ].…”