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

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.

In vivo biological evaluation of sodium salt of ethyl (E)‐2‐cyano‐3‐(7‐hydroxy‐4‐methyl‐2‐oxoquinoline‐1(2H)‐yl)‐3‐(4‐hydroxyphenyl) acrylate as anticancer agent

“…25 Our outcomes disclosed that the average value of total antioxidant capacity in the liver tissue was 0.311 ± 0.110 (mM/L) for negative control group. This value slightly reduced to 0.305 ± 0.003 Our outcomes agree with those of Mohammed et al, 27 who synthesized a hybrid molecule comprising coumarin and quinolinone moieties and evaluated the total antioxidant capacity in liver and kidney tissues of EAC-bearing mice. The findings revealed a strong anti-tumour effect against EAC cells by the inducement of antioxidant activities.…”

“…These findings are inconsistent with Mohammed et al, 27 who declared a considerable diminish in albumin levels in the EACinoculated group compared to the normal group. Treatment with the hybrid atoms of coumarin and quinolinone leads to a considerable rise of albumin for both therapeutic and preventive groups compared to the EAC-inoculated group.…”

“…Our outcomes displayed that treatment with the sodium salt of the compound displayed a highly considerable diminished in the activity Mohammed et al, 27 declared that the administration of quinoline compounds caused a significant reduction in ALT and AST activities.…”

“…The outcomes asserted that albumin level was enhanced in all groups that took this treatment. 27 Kumar et al, 22 reported that total protein levels in the serum were increased in EAC-inoculated animals. Treatment with quinoline compounds significantly reverted such a rise.…”

“…In accordance, the therapeutic and preventive groups of the present study showed a significant decrease in AST and ALT activities compared to the EAC-inoculated group. 27 Reliable laboratory tests for renal functions are vital for the pre-emptive recognition of renal failure, detection and monitoring renal diseases. Urea and creatinine are final nitrogenous yields of metabolism.…”