Introduction: The ability of to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by . Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity. Chromone 5-maleimide substitution compounds (CM3a) showed favorable antibacterial activity against .
Methods: CM3A with antibacterial activity was synthesized and screened. The minimum inhibitory concentration (MIC) of CM3a were determined by the broth microdilution method. Biofilm eradication assay and colony count methods were used to investigate the effect of CM3a on biofilm disruption and killing. Changes in biofilm architecture when subjected to CM3a, were visualized using confocal laser scanning microscopy (CLSM). CCK-8 assay and survival rate of larvae were used to test the toxicity of CM3a.
Results: The minimum inhibitory concentration (MIC) of CM3a against was about 26.4 μM. Biofilm staining and laser scanning confocal microscopy analysis showed that CM3a eradicated biofilms by reducing the viability of the constituent bacterial cells. On the other hand, CM3a showed negligible toxicity against mouse alveolar epithelial cells and larvae.
Conclusion: Chromone derivatives CM3a has therapeutic potential as a safe and effective compound for the treatment of infection.
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http://dx.doi.org/10.2147/IDR.S301483 | DOI Listing |
Infect Drug Resist
March 2021
Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200082, People's Republic of China.
Introduction: The ability of to form biofilms is associated with high mortality and treatment costs. Established biofilms cannot be eradicated by many conventional antibiotics due to the development of antibiotic tolerance by . Here we report the synthesis and biological characterization of novel small-molecule compounds with antibiofilm activity.
View Article and Find Full Text PDFJ Comput Chem
October 2011
Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, USA.
Scaling factors for atomic charges derived from the RM1 semiempirical quantum mechanical wavefunction in conjunction with CM1 and CM3 charge models have been optimized by minimizing errors in absolute free energies of hydration, ΔG(hyd) , for a set of 40 molecules. Monte Carlo statistical mechanics simulations and free energy perturbation theory were used to annihilate the solutes in gas and in a box of TIP4P water molecules. Lennard-Jones parameters from the optimized potentials for liquid simulations-all atom (OPLS-AA) force field were utilized for the organic compounds.
View Article and Find Full Text PDFJ Phys Chem B
August 2008
Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, Qinghai 810001, China.
In order to explore the inhibitory mechanism of coumarins toward aldose reductase (ALR2), AutoDock and Gromacs software were used for docking and molecular dynamics studies on 14 coumarins (CM) and ALR2 protease. The docking results indicate that residues TYR48, HIS110, and TRP111 construct the active pocket of ALR2 and, besides van der Waals and hydrophobic interaction, CM mainly interact with ALR2 by forming hydrogen bonds to cause inhibitory behavior. Except for CM1, all the other coumarins take the lactone part as acceptor to build up the hydrogen bond network with active-pocket residues.
View Article and Find Full Text PDFJ Comput Chem
August 2004
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
Absolute free energies of hydration (DeltaGhyd) have been computed for 25 diverse organic molecules using partial atomic charges derived from AM1 and PM3 wave functions via the CM1 and CM3 procedures of Cramer, Truhlar, and coworkers. Comparisons are made with results using charges fit to the electrostatic potential surface (EPS) from ab initio 6-31G* wave functions and from the OPLS-AA force field. OPLS Lennard-Jones parameters for the organic molecules were used together with the TIP4P water model in Monte Carlo simulations with free energy perturbation theory.
View Article and Find Full Text PDFArch Biochem Biophys
March 1997
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Northern blot and immunoblot analyses indicated that considerable levels of CYP2B, CYP2C, CYP2D, CYP2E, and CYP3A were expressed in the liver of untreated marmosets. CYP1A was also expressed but to lesser extents. CYP3A mRNA was also detectable in the small intestine of untreated marmoset; the amount was increased by treatment with polychlorinated biphenyl.
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