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

•A novel family of spirocyclic aminopyrimidine derivatives was synthesized.•The antibacterial activity of these compounds was investigated against different bacterial pathogens including multi-drug resistant strains.•Compounds 4, 6, 8e were found to possess potent antibacterial activity.•Compound 6...

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Bibliographic Details
Published in:Journal of molecular structure 2023-04, Vol.1278, p.134912, Article 134912
Main Authors: Ragab, Sherif S., Abdelraof, Mohamed, Elrashedy, Ahmed A., Sweed, Ayman M.K.
Format: Article
Language:English
Subjects:
Antibacterial
Molecular dynamics
Multidrug resistance
Schiff bases
Spirocyclic
Triazolopyrimidine
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Summary:•A novel family of spirocyclic aminopyrimidine derivatives was synthesized.•The antibacterial activity of these compounds was investigated against different bacterial pathogens including multi-drug resistant strains.•Compounds 4, 6, 8e were found to possess potent antibacterial activity.•Compound 6 exhibited the highest activity in terms of MIC values compared to ciprofloxacin.•Molecular dynamic simulations and docking studies were investigated. The rise of new bacterial pathogens that ascribed as multi-drug resistant became a major concern, particularly in the medical sectors. In the current study, we designed novel molecular hybrids based on spirocyclic 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 addition 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 docking 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. [Display omitted]
ISSN:0022-2860
1872-8014
DOI:10.1016/j.molstruc.2023.134912