ABSTRACT
New quinoline-3-carbonitrile derivatives were synthesized and evaluated for their potential antibacterial behavior. Compounds were obtained by a one-pot multicomponent reaction of appropriate aldehyde, ethyl cyanoacetate, 6-methoxy-1,2,3,4-tetrahydro-naphthalin-1-one and ammonium acetate. Structures were established by different physical and spectroscopic techniques. The molecular geometry, vibration frequencies, HOMO-LUMO energy gap, molecular hardness (g), ionization energy (IE), electron affinity (EA), and total energy of these compounds was assessed by DFT studies, employing DFT/RB3LYP method. Preliminary antibacterial studies using both Gram-positive and Gram-negative bacterial strains and cytotoxicity studies on mammalian cells revealed their promising antibacterial activity, without causing any severe host toxicity. All the compounds (QD1-QD5) in this study obeyed the 'Lipinski's Rule of Five' with logP values <5 and HBA <10, hydrogen bond donor's <5. The most active compound QD4 showed good interaction with the target DNA gyrase; target enzyme for quinoline class of antibiotics, which reveals its probable mechanism of action. Results of all these studies establish these compounds as important scaffolds with broad-spectrum antibacterial activity with no off-target toxicity. Having lower band gap energy of 3.40â¯eV and a low lying LUMO for compound QD4, this compound may be a valuable starting point for the development of quinoline-3-carbonitrile based broad-spectrum antibacterial agents.
Subject(s)
Anti-Bacterial Agents/pharmacology , Escherichia coli/drug effects , Quinolines/pharmacology , Salmonella typhimurium/drug effects , Staphylococcus aureus/drug effects , Streptococcus pyogenes/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Density Functional Theory , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Quinolines/chemical synthesis , Quinolines/chemistry , Structure-Activity RelationshipABSTRACT
Two push-pull chromophores were synthesized by knoevenagel condensation under microwave irradiation. The structure of synthesized chromophores were established by spectroscopic (FT-IR, (1)H NMR, (13)C NMR, EI-MS) and elemental analysis. Structure of the chromophores was further conformed by X-ray crystallographic. UV-Vis and fluorescence spectroscopy measurements provided that chromophores were good absorbent and fluorescent properties. Fluorescence polarity studies demonstrated that chromophores were sensitive to the polarity of the microenvironment provided by different solvents. Physicochemical parameters, including singlet absorption, extinction coefficient, stokes shift, oscillator strength, dipole moment and flurescence quantum yield were investigated in order to explore the analytical potential of the synthesized chromophores. In addition, the total energy, frontier molecular orbitals, hardness, electron affinity, ionization energy, electrostatic potential map were also studied computationally by using density functional theoretical method.
Subject(s)
Chemical Phenomena , Coloring Agents/chemistry , Coloring Agents/chemical synthesis , Microwaves , Quantum Theory , Carbazoles/chemistry , Chemistry Techniques, Synthetic , Crystallography, X-Ray , Fluorescence Polarization , Models, Molecular , Molecular ConformationABSTRACT
Chalcones were synthesized by reaction of 3-acetyl-2,5-dimethylfuran with corresponding active aldehyde in ethanolic NaOH. The structure of these compounds was established by elemental analysis, IR, (1)H-NMR, (13)C-NMR and EI-MS spectral analysis. UV-vis and fluorescence spectroscopy measurements provided that compounds are good absorbent and fluorescent. Fluorescence polarity study demonstrated that the compounds were sensitive to the polarity of the microenvironment provided by deferent solvents. In addition, spectroscopic and physicochemical parameters, including electronic absorption, extenction coefficient, Stokes shift, oscillator strength and transition dipole moment were investigated in order to explore the analytical potential of synthesized compounds. The anti-bacterial activity of the compounds were first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined with the reference of standard drug Tetracycline. The results showed that compound 3 is better inhibitors of both types of the bacteria (Gram-positive and Gram-negative) as compared to tetracycline. Graphical Abstract á .