Synthesis and in Silico Biological Activity of Novel Bridged Systems based on 5-Formyl Derivatives Oof Pyrimidine-4,6-Diols

Abstract

The growing body of publications on the synthesis of 1,3-diazine-bridged systems has drawn increasing attention to these compounds. The aim of our work was to synthesise novel bisazomethines derived from 4,6-dihydroxy-2-methylpyrimidine-5-carbaldehyde (1). A series of Schiff bases was obtained via nucleophilic addition of aliphatic diamines to the carbonyl group of substrate�1. Water was employed as the sole solvent during synthesis, affording target products in 85�90% isolated yields. Structural confirmation was achieved by �H and ��C nuclear magnetic resonance (NMR) spectroscopy. In silico screening (PASS Online, CLC-pred, Antivir-pred, and GUSAR Online) revealed that the synthesised bisazomethines exhibit broad-spectrum bioactivity, including antihypertensive, antibacterial, and anticancer properties, while maintaining Class 4 toxicity (low risk). Thus, we report novel bridged bisazomethines based on a 5-formyl derivative of� 2-methylpyrimidine-4,6-diol, which combine a promising safety profile with multifaceted biological activity.