In Vivo Biological Evaluation of Ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1- ylamino)-coumarin-3-carboxylate as an Antitumor Agent

Faculty Science Year: 2020
Type of Publication: ZU Hosted Pages:
Authors:
Journal: Anti-Cancer Agents in Medicinal Chemistry. Anti-Cancer Agents in Medicinal Chemistry Volume:
Keywords : , Vivo Biological Evaluation , Ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1- ylamino)-coumarin-3-carboxylate    
Abstract:
Background Hybridization of coumarin moiety with additional antitumor pharmacophores is an auspicious stratagem to afford precious therapeutic interference for the medication of cancer. Objective The present study aimed to evaluate the antitumor activity of ethyl 4-(7-hydroxy-4-methyl-2-oxoquinolin-1- ylamino)-coumarin-3-carboxylate against Ehrlich ascites carcinoma (EAC) cells in the peritoneal cavity of female mice. Methodology Molecular docking was used to predict the binding between the test compound and the receptor of breast cancer mutant 3HB5-oxidoreductase.The viability of tumor cells and life span prolongation. Total antioxidant capacity was evaluated in the liver and kidney. Serum alanine transaminase, aspartate transaminase, albumin, total protein, creatinine, and urea were estimated. The concentrations of Bcl-2 and Bax were measured in the liver and kidney tissues. Histopathological examination of the liver and kidney tissues was carried out. Results EAC-bearing mice injected with the test compound showed a highly significant decrease in tumor cell viability by 100% compared to EAC control. Also, it exhibited significant antioxidant and apoptotic agents through the results of total antioxidant capacity and apoptosis assays. Confirmed by histological examination, the results of the liver and kidney function tests revealed that the test compound has no harmful effect on both two organs. The docking investigation disclosing an auspicious interaction between the test compound and the receptor (3HB5). To confirm our results, correlations between different parameters were carried out. We found that there were significant positive and negative correlations between parameters. Conclusion Hybrid molecules containing coumarin and quinolinone exhibited potential antitumor effect against EAC cells by induction of apoptosis and antioxidant activities. Results of liver and kidney function tests and the histopathological study revealed that the administration of the test compound nullified most of the pathological alterations induced by EAC cells in mice. Based on these findings, the test compound can be developed as an effective chemotherapeutic agent.
   
     
 
       

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