Synthesis, Characterization, Antimicrobial Screening, and Computational Studies of a Tripodal Schiff Base Containing Pyrimidine Unit

Abstract

A novel tripodal Schiff base ligand, 5‐amino‐2,4,6‐tris(4‐carboxybenzimino)‐1,3‐pyrimidine (TTPS), was synthesized for the first time by the reaction of 2,4,5,6‐tetraaminopyrimidine with 4‐carboxybenzaldehyde. The ligand was characterized by means of ultraviolet–visible, Fourier transform infrared, one‐dimensional 1H‐NMR, and one‐dimensional 13C‐NMR spectroscopies and elemental microanalysis. The Fourier transform infrared and NMR studies revealed that one of the NH2 group in 2,4,5,6‐tetraaminopyrimidine is not involved in bonding. The in vitro antimicrobial activities of the ligand were investigated against Gram‐negative bacteria: Escherichia coli (ATCC 6749) and Pseudomonas aeruginosa (ATCC 9027), Gram‐positive bacteria: Staphylococcus aureus (ATCC 6538P) and Bacillus cereus (ATCC 14579), and fungi: Candida albicans and Aspergillus niger by the agar well diffusion technique. TTPS exhibits good activity against the test microorganisms. The minimum inhibitory concentrations of TTPS against S. aureus were compared with tetracycline and gentamicin, which are conventional bacterial drugs. The upper level of Lorke's method was used to determine the acute toxicity of the compound. The acute toxicity test indicates that TTPS is toxic at doses above 2154 mg/kg. The in vivo antimalarial assay was carried out on Plasmodium berghei based on the 4‐day suppressive method. The result shows a general dose‐dependent significant parasitemia inhibition compared with the negative control with TTPS having inhibition of 72.20% at 50 mg/kg and 65.81% at 25 mg/kg close to the value (87.22%) of the standard drug artesunate 5 mg/kg. Density functional theory method was used to complement this experimental investigation.