Synthesis, Biological Evaluation and Principal Component Analysis of Arylidene Analogues of Barbituric Acid Obtained via Knoevenagel Condensation

The synthesis of 5-arylidene barbiturates has been extensively documented through various methodologies. In this study, we synthesized ten derivatives of barbiturate 5-arylidenes using an optimized Knoevenagel reaction catalyzed by a synthetic enzyme supported in chloride ionic liquids, achieving satisfactory yields ranging from 68 to 97%. Upon evaluating the biological properties of these ten compounds, derivative 12 (5-(2-hydroxy)benzylidene of acid barbituric), a nitro compound, exhibited broad-spectrum bactericidal activity against both the Gram-negative bacterium Escherichia coli and the Gram-positive bacillus Bacillus subtilis. Furthermore, it demonstrated moderate fungistatic activity against Candida albicans. Additionally, derivatives 10 (5-benzylidene of acid barbituric) and 11 (5-(3-nitro) benzylidene of acid barbituric) displayed antioxidant activity comparable to that of the positive control quercetin, albeit only at the highest concentration tested (400 µg mL-1). This study integrates quantum chemistry calculations with multivariate statistical methods, specifically principal component analysis, to correlate theoretical descriptors with the antibacterial and fungicidal activities of the compounds. In conclusion, given the promising outcomes of this investigation and recognizing the scarcity of studies delving into the biological properties of 5-arylidene barbiturate compounds, it is suggested that future research should explore other biological and pharmacological aspects of these compounds.