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Area of Science:

  • Medicinal Chemistry
  • Toxicology
  • Pharmacology

Background:

  • Drug discovery faces challenges including adverse effects and inefficacy.
  • Heterocyclic compounds derived from coumarin offer potential therapeutic avenues.

Purpose of the Study:

  • To investigate the acute toxicity of novel coumarin derivatives, coumacine I and coumacine II.
  • To evaluate the impact of these compounds on renal and hepatic function in a mouse model.

Main Methods:

  • Acute toxicity study using a mouse model (n=25).
  • Administration of coumacine I and coumacine II at 1000 mg/kg and 2000 mg/kg single doses.
  • Biochemical analysis of serum for renal function (creatinine, urea) and liver enzymes (GOT, GPT).
  • Histopathological examination of kidney and liver tissues.

Main Results:

  • High doses (2000 mg/kg) of coumacine I and coumacine II significantly increased serum creatinine, urea, GOT, and GPT levels (p<0.05).
  • Histopathological analysis revealed deleterious changes in kidney and liver tissues at high doses.
  • Compounds demonstrated relative safety at lower doses, comparable to therapeutic coumarin doses.

Conclusions:

  • Coumacine I and coumacine II exhibit a dose-dependent toxicity profile.
  • High doses of these novel coumarin derivatives can induce significant renal and hepatic toxicity.
  • Further studies are warranted to establish safe therapeutic windows for coumacine I and coumacine II.