A Novel Preparation, Identification and Bioactivity Analysis of Schiff and Mannich Bases Based on Flucytosine Compounds

Herein, an innovative and sustainable process was used to create a series of eight novel flucytosine derivatives. The flucytosine drug was employed to synthesize several new heterocyclic Schiff base compounds. Specifically, flucytosine was utilized to produce two new Schiff base derivatives: 5-fluoro-4-((4-hydroxybenzylidene) amino) pyridin-2(1H)-one (R1) and (E)-5-fluoro-4-((1-(4-hydroxyphenyl)ethylidene)amino)pyridin-2(1H)-one (R2). These Schiff bases, R1 and R2, synthesized in the initial step, contain an (NH) group that reacts with isatin, diethylamine, and diphenylamine to produce six Mannich bases (R3-R8). Thin-layer chromatography (TLC) was used to monitor each reaction. The synthesized compounds were characterized using Fourier-Transform-Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR) spectroscopy, and their physical properties, including yield percentage and melting points, were determined. Bioactivity analysis demonstrated that all compounds exhibited efficacy against the tested microorganisms. The first Schiff base, R1, showed superior antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli compared to the other compounds. Notably, R1 exhibited significantly stronger antibacterial properties against E. faecalis, while compound R8 showed lower activity against S. aureus, and E. coli. These antibacterial properties are attributed to the presence of an electron-withdrawing group in the aryl moiety, highlighting the potential of these compounds in the development of new antimicrobial drugs.