SYNTHESIS, ANTIMICROBIAL SCREENING AND MOLECULAR DOCKING STUDY OF SOME NEW PYRIMIDIN2-AMINE DERIVATIVES AS POSSIBLE BIOACTIVE AGENTS

A novel series of 4, 6-disubstituted pyrimidin-2-amine derivatives (5a–f) was synthesized in good yields via a cyclocondensation reaction of chalcone-based intermediates (4a–f) with guanidine hydrochloride using sodium methoxide as the base. The key intermediates, N'-(5-(3-(2,4-disubstituted phenyl)-3-oxoprop-1-enyl)-4-(4- bromophenyl)-6-(3,4-disubstituted phenyl) pyrimidin-2-yl)-N, N-dimethylformamidine derivatives (4a–f), were prepared from aryl and heteroaryl acetophenones (3a–c) and 4,6-diaryl-substituted pyrimidine-5-carboxaldehydes (2a–b) via Claisen–Schmidt condensation. The structures of the synthesized compounds were confirmed through spectroscopic techniques, including IR, ¹HNMR, ¹³CNMR, mass spectrometry, and elemental analysis. The synthesized compounds were evaluated for their in vitro antibacterial activity against E. coli (Gram-negative) and S. aureus (Gram-positive). Notably, compounds exhibited significant inhibitory activity against E. coli, with compound 5a demonstrating superior performance, whereas moderate to poor activity was observed against S. aureus. Furthermore, molecular docking studies were conducted using the E. coli DNA gyrase B protein (PDB ID: 1KZN) to investigate the binding affinities of the ligands. Compounds 5a and 5b showed the highest docking scores and favourable binding interactions at the active site, correlating well with their biological activity. These results suggest that pyrimidin-2-amine derivatives, particularly 5a and 5b, represent promising candidates for the development of potent antibacterial agents targeting Gram-negative pathogens.