Access to new Schiff bases tethered with pyrazolopyrimidinone as antibacterial agents: Design and synthesis, molecular docking and DFT analysis

• Published in: Journal of molecular structure 2022-01, Vol.1248, p.131523, Article 131523
• Main Authors: Horchani, Mabrouk, Edziri, Hayet, Harrath, Abdel Halim, Jannet, Hichem Ben, Romdhane, Anis
• Format: Article
• Language: English
• Subjects: Antibacterial; DFT calculation; Docking; Pyrazolopyrimidinones; RAS; Schiff bases
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2021.131523

•A series of new Schiff bases tethered with pyrazolopyrimidinones was synthesized and characterized.•All compounds were evaluated in vitro for their antibacterial activity towards six microorganisms.•Several compounds exhibited significant antibacterial activity.•Docking studies for crystallized structures of B. subtilus (6CGQ) and P. aeruginosa (6P8U) confirmed the activity of some derivatives.•HOMO-LUMO energy gap and MEP are calculated using DFT/B3LYP/6–311++G(d, p) method. In the present study, a new series of Schiff bases (4a-h) were designed and synthesized via the treatment of the previously prepared 5-aminopyrazolopyrimidinone 3 with a series of differently substituted arylaldehydes. Compound 3 was obtained from the condensation of pyrazolo[3,4-d]pyrimidinone 2 with hydrazine monohydrate. The structures of the newly prepared compounds (4a-h) were confirmed on the basis of their 1H, 13C NMR and ElectroSpray-High Resolution Mass Spectrometry ES-HRMS data. All target compounds were screened in vitro for their antibacterial activity towards three Gram-positive and three Gram-negative strains. The results indiacted that the derivative 4d (R = 4-CH3) exhibited the better inhibitory potential against most bacteria and notably towards B. subtilus and S. aureus with MIC values of 7.60 and 31.25 μg/mL, respectively. Moreover, compound 4c (R = 4-Cl) displayed the highest activity towards Acinitobacter CI with (MIC= 7.81 μg/mL). Besides, molecular docking studies for crystallized structures of the threonine synthase from B. subtilis ATCC 6633 and nucleotidyltransferase (chain A) from P. aeruginosa ATCC 27,853 enzymes highlighted high binding affinity of all synthesized compounds 4 especially ligand 4d and the detected interactions and scoring were found to be in good agreement with the experimental results. Furthermore, The molecular geometry of all derivatives are studied theoretically using the Density Functional Theory (DFT) method with B3LYP/ 6- 311++G(d,p). [Display omitted]