Sonosynthesis of new functionalized optically active triazines via double Mannich reaction: antibacterial potential and in silico docking study

Abstract

In this study, we employed both conventional and ultrasound irradiation approaches to fabricate a library of ten new triazine hybrids by the divergent double-Mannich reaction. The titled compounds were characterized by extensive spectral analyses, including IR, MS, 1D NMR (1H, ¹³C, ¹⁵N, ¹⁹F), and 2D NMR (DEPT135, HSQC). Additionally, their antibacterial activity against a spectrum of bacterial strains, encompassing two Gram-positive and two Gram-negative bacteria, was assessed. Notably, compound 9 emerged as the most potent antibacterial agent with an inhibition zone of 39 mm against Bacillus subtilis, 50 mm against Staphylococcus epidermidis, 41 mm against Enterobacter cloacae, and 40 mm against Escherichia coli. Moreover, molecular docking simulation demonstrated the responsible binding affinity of the synthesized scaffolds with target proteins (PDB: 1OF0, 8P20, 1KQB, 1KZN). Likewise, structure–activity relationship (SAR) studies of the newly synthesized triazine derivatives demonstrated that substituent identity significantly impacts antibacterial activity. Notably, compound 9, bearing chloro and fluoro atoms, exhibited the highest antibacterial activity among all tested derivatives. Furthermore, optical activity measurements were performed through a polarimeter to confirm the tetrahedral stereocenter of nitrogenous scaffolds.