Design, synthesis, molecular dynamic simulation studies, and antibacterial evaluation of new spirocyclic aminopyrimidines

The rise of new bacterial pathogens that ascribed as multi-drug resistant became a major concern, partic-ularly in the medical sectors. In the current study, we designed novel molecular hybrids based on spiro-cyclic pyrimidine which feature either triazolo ring or various functionalities such as alkyl, hydrazino, azomethine motifs. The newly synthesized spirocyclic pyrimidines were screened for their bactericidal activities against some bacterial pathogens such as Salmonella typhimurium and Proteus vulgaris in addi-tion to the multi-drug resistant Pseudomonas aeruginosa and Staphylococcus aureus (MRSA). Compounds coded 4, 6 , and 8e were found to possess potent bactericidal activities compared to the standard drugs (Ciprofloxacin and Cephradine). Interestingly, compound 6 exhibited the highest antibacterial activity with low MIC value close to that obtained for ciprofloxacin. Molecular dynamic simulations and dock-ing studies were investigated to check the performance of our compounds upon binding to the protein active sites as well as their interactions and stabilities through the simulation process.(c) 2023 Elsevier B.V. All rights reserved.