ACUTE TOXICITY OF COUMACINES: AN IN VIVO STUDY

The design and synthesis of new drugs are increasingly challenging in chemistry settings. The synthesis is itself lured by the properties of the product after synthesis, including solubility, hygroscopicity, intensive adverse effects, and biological inefficacy; hence, the creation of a new drug should be considered in light of the avoidance of these downside features, if any. The present study is designed to investigate the acute toxicity of newly discovered heterocyclic frameworks derived from the coumarin backbone, namely coumacine I and coumacine II. To do so, a mouse model of 25 mice was subclassified into 5 groups (5 mice control, 5 mice coumacine I 1000 mg/kg, 5 mice coumacine II 1000 mg/kg, 5 mice coumacine I 2000 mg/kg, and 5 mice coumacine II 2000 mg/kg), a single dose was given, and mice were sacrificed after 4 hours post-dose. The blood sample and tissue were collected for biochemical and histopathological studies. Serums were analyzed for the measurement of renal function and liver enzyme activity using classical biochemical methods. A high dose of either compound caused deleterious changes, as evidenced by a significant (p<0.05) increase in creatinine, urea, GOT, and GPT, as well as disrupting tissue quasi-equilibrium at the cellular level in both kidney and liver. To sum up, coumacine I and coumacine II are relatively safe unless otherwise used in high doses, knowing that either dose in the present study is remarkably higher than the therapeutic dose of coumarins currently in use in clinical settings.