Synthesis, antibacterial activities, and theoretical studies of dicoumarols

• Published in: Organic & biomolecular chemistry 2014-08, Vol.12 (29), p.5528-5535
• Main Authors: Li, Jing, Hou, Zheng, Chen, Guang-Hui, Li, Fen, Zhou, Ying, Xue, Xiao-Yan, Li, Zhou-Peng, Jia, Min, Zhang, Zi-Dan, Li, Ming-Kai, Luo, Xiao-Xing
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Cell Death; Crystallography, X-Ray; Dicumarol - chemical synthesis; Dicumarol - chemistry; Dicumarol - pharmacology; Dicumarol - toxicity; Electrons; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Hydrogen Bonding; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - growth & development; Microbial Sensitivity Tests; Models, Molecular; Quantum Theory; Staphylococcus; Static Electricity; Thermodynamics
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c4ob00772g

Four dicoumarols (DC, 2-PyDC, 3-PyDC and 4-PyDC) were synthesized and characterized via IR, (1)H NMR, HRMS, and single crystal X-ray crystallography. Two classical intramolecular O-H···O hydrogen bonds (HBs) stabilized their structures. The total HB energies in DC, 2-PyDC, 3-PyDC and 4-PyDC were calculated with the density functional theory (DFT) [B3LYP/6-31G*] method. The in vitro antibacterial activity of DC, 2-PyDC, 3-PyDC and 4-PyDC against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), and USA 300 (Los Angeles County clone, LAC) was evaluated by observing the minimum inhibitory concentration and time-kill curves. The results showed that among all the compounds, 2-PyDC exhibited the most potent antibacterial activity.