Quinoline‐based thiazolidinone derivatives as potent cytotoxic and apoptosis‐inducing agents through EGFR inhibition. (19th December 2021)

• Record Type: Journal Article
• Authors: Nafie, Mohamed S.; Kishk, Safaa M.; Mahgoub, Sebaey; Amer, Atef M.
• Is Part Of: Chemical biology & drug design. Volume 99:Number 4(2022)
• Page Start: 547
• Page End: 560
• Publication Date: 2021-12-19
• Subjects: apoptosis -- docking -- EGFR inhibition -- in vivo -- quinoline‐based thiazolidinone; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13997
• Languages: English
• ISSNs: 1747-0277

Abstract

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 IC50 value of 7.43 µM compared to 5‐FU (IC50 = 11.36 µM) with moderate cytotoxic activity against the FHC (IC50 = 35.27 µM), and it exhibited remarkable inhibition activity of EGFR with IC50 value of 96.43 nM compared to Erlotinib (IC50 = 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. Abstract : Compound 7 was investigated as an anticancer agent through epidermal growth factor receptor (EGFR) in three integrated approaches in vitro, in vivo, and in silico. It exhibited cytotoxic activity against HCT‐116 with an IC50 value of 7.43 µM compared to 5‐FU (IC50 = 11.36 µM) with non‐cytotoxic activity against the FHC (IC50 = 35.27 µM). It exhibited remarkable EGFR inhibition with an IC50 value of 96.43 nM compared to Erlotinib (IC50 = 78.65 nM). It significantly stimulated apoptotic colon cancer cell death with 171.58‐fold arresting cell cycle at the G2 and S‐phases. It ameliorated the both biochemical and histochemical structures near normal with tumor inhibition ratio of 52.92% compared to 5‐FU of 57.16%. It was docked inside the ligand‐binding site of EGFR with good binding energy and an interactive profile.