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Updated: Jun 7, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
A facile one-pot synthesis to access unique benzopyranonyl cyanopyrimidinols with multitargeting potential against
Ping-Ping Duan1, Li Wang1, Zhen-Zhen Li1
1Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
Abstract:
To combat rising antimicrobial resistance, a class of novel cyanopyrimidinols (CPOs) were designed and synthesized via a three-component one-pot reaction strategy. Several prepared CPOs exhibited strong antibacterial activity against the tested bacteria. Especially, benzopyranonyl CPO 4 demonstrated potent activity against Enterococcus faecalis p1-2007226001 (MIC = 0.001 mM), displaying 6- and 64-fold lower MIC values than norfloxacin (MIC = 0.006 mM) and sulfadiazine (MIC = 0.064 mM). CPO 4 showed negligible hemolysis and lower resistance propensity than norfloxacin. In silico ADME analysis revealed favorable drug-likeness and pharmacokinetics of compound 4. Moreover, the highly active molecule CPO 4 displayed superior in vivo antibacterial activity to norfloxacin in Galleria mellonella infection model. Further investigation suggested that CPO 4 could intercalate into DNA to form a CPO 4 - DNA complex, thereby blocking DNA replication, while also disrupting bacterial metabolism and inducing intracellular protein leakage. These findings highlighted cyanopyrimidinols as novel scaffolds for developing multitargeting antibacterial agents.
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