Exploiting the Thiobarbituric Acid Scaffold for Antibacterial Activity

Thiobarbituric acid (TBA) has been considered a privileged structure for developing antimicrobial agents. Diversity was obtained at positions N and at C5 through acylation, Schiff base formation, Knoevenagel condensation, and thioamide and enamine formation. The present work describes the synthesis of small libraries based on the TBA moiety and above‐mentioned reactions. Preliminary antimicrobial activity screening of the prepared compounds against selected bacteria (both Gram‐positive and ‐negative) showed the best results for the Boc‐Phe‐TBA derivative. These results could be useful for designing and building libraries based on other amino acids with distinct protecting groups. Antimicrobial analogue insight: Thiobarbituric acid (TBA) analogues with various functionalities at positions N and C5 were synthesized by acylation, Knoevenagel condensation, Schiff base, thioamide and enamine formation. They were then evaluated for antimicrobial activity, and Boc‐protected amino acid conjugates at position C5 with an ethyl‐substituted nitrogen atom were found to afford the best results; these could be useful in the design of future TBA‐based derivatives.