Synthesis, Breast Anticancer Activity and Theoretical Studies of Some New Barbituric Acid Derivatives

Abstract

A series ofnew barbituric acid derivatives containing heterogeneous rings such as pyrazolines (7-21), oxazolines (22-26) and oxiranes (27-31) have been prepared by reacting barbituric acid with some aldehydes to prepare chalcones (2-6) and then reacting the latter with aqueous hydrazine, phenylhydrazine, hydroxyamine hydrochloride and hydrogen peroxide. These derivatives were obtained by exploiting the presence of an active carbon atom (C5) in the structure of the starting material (barbituric acid) carrying an acidic hydrogen atom that provides the carbanion ion that enters into the aldol condensation to produce a number of -unsaturated carbonyl compounds (2-6). After confirming the chemical formulas of the prepared compounds (2-31) by conducting some physical and spectral measurements, some theoretical studies were conducted on the starting material (1) and the prepared compounds (2-31) to predict their pharmacokinetic properties through (Swiss ADME evaluation) and to predict the extent of their toxicity to heart functions through (cardiotoxicity) test. Finally, in light of the previous results, the two compounds (25, 30) were selected to perform (cytotoxicity test), and the results were positive, i.e. the two selected compounds inhibited the growth of breast cancer cells (MCF-7) versus very slight inhibition of healthy cells of the type (HDFN) taken from neonatal dermal fibroblast cells.