Lucia Pintilie

By Pintilie Lucia

Part of the book: Antimicrobial Agents

By Pintilie Lucia

The emergence of resistance to antimicrobial agents is a global public health problem. Some microorganisms may develop resistance to a single antimicrobial agent (or related class of agent), while others develop resistance to several antimicrobial agents or classes. These organisms are often referred to as multidrug-resistant or MDR strains. Identification of new molecules that show activity against multidrug-resistant microorganisms and its development on a new antimicrobial drug, would be an important step in the fight against antimicrobial resistance. This paper presents experimental data regarding the synthesis of several quinolones. The novel compounds having quinolone structure were synthesized by Gould-Jacobs method. Their structure has been determined and confirmed by the following physicochemical methods: elemental analysis, IR spectral analysis, H-NMR, C-NMR, UV, thin layer chromatography. The new compounds have been evaluated for „in vitro” activity by determining minimum inhibitory concentration against a variety of bacteria Some of new quinolones, which showed a good activity, have been tested against 30 strains of methicillin resistant Staphylococcus aureus isolated in the Microbiology Laboratory of INBI Prof. “Dr. Matei Bals” during 2012 The minimum inhibitory concentration (MIC) of the isolates have been determined by agar plate Mueller Hinton (bioMerieux) dilution method using the reference strain Staphylococcus aureus ATCC 29213. The 30 strains of isolated have been also tested for susceptibility to ciprofloxacin, levofloxacin and imipenem by Etest method. Base on the “in vitro” studies, the quinolone FPQ-30 appears to be an promising compound, all strains isolates were inhibited at a concentration of 8 μg/ml.

Part of the book: Concepts, Compounds and the Alternatives of Antibacterials

By Amalia Stefaniu and Lucia Pintilie

The main goal of this chapter is to reveal the importance of molecular structure analysis with specific computational tools using quantum chemistry methods based on density functional theory (DFT) with focus on pharmaceutical compounds. A wide series of molecular properties and descriptors related with chemical reactivity is discussed and compared for small organic molecules (e.g., quinolones, oxazolidinones). Structural and physicochemical information, important for quantitative structure-property relationships (QSPR) and quantitative structure-activity relationships (QSAR) modeling analysis, obtained using Spartan 14 software Wavefunction, are reported. Thus, by a computational procedure including energy minimization and predictive calculations, values of quantum chemical parameters and molecular properties related with electronic charge distribution are reported and discussed. Frontier molecular orbitals energy diagram and their bandgap provide indications about chemical reactivity and kinetic stability of the molecules. Derived parameters (ionization potential (I), electron affinity (A), electronegativity (χ), global hardness (η), softness (σ), chemical potential (μ) and global electrophilicity index (ω)) are given. Also, graphic quantities are reported: electrostatic potential maps, local ionization potential maps and LUMO maps, as visual representation of the chemically active sites and comparative reactivity of different constitutive atoms.

Part of the book: Symmetry (Group Theory) and Mathematical Treatment in Chemistry

By Lucia Pintilie and Amalia Stefaniu

Molecular docking studies have been carried out for a better understanding of the drug-receptor interactions. All the synthesized compounds have been subjected to molecular docking against targets that have been chosen based on the specific mechanism of action of the quinolones used in the antibacterial activity screening. A study of the characteristics and molecular properties of the small molecule known as ligand has been realized. In the first stage of the study, the 2D and 3D structures have been generated. The most stable conformer for each structure was obtained by geometry optimization and energy minimization. A series of topological, conformational characteristics and QSAR properties, important to assess the flexibility and the ability of the studied conformer to bind to the protein receptor, were determined and analyzed. These properties were discussed in order to assess the flexibility and the binding ability of studied conformers to bind to the receptor protein. The docking studies have been carried out. The score and hydrogen bonds formed with the amino acids from group interaction atoms are used to predict the binding modes, the binding affinities and the orientation of the docked quinolones in the active site of the protein receptor.

Part of the book: Molecular Docking

By Lucia Pintilie and Amalia Stefaniu

Quinolones are an important class of heterocyclic compounds that possess interesting biological activities like antimicrobial, antitubercular, and antitumor. The objective of this study is to evaluate in silico the antitumoral and antimycobacterial activity of some quinolone derivatives by using CLC Drug Discovery Workbench Software. Docking studies were carried out for all ligands, and the docking scores were compared with the scores of standard drugs, topotecan and levofloxacin. The docking studies have been carried out to predict the most possible type of interaction, the binding affinities, and the orientations of the docked ligands at the active site of the target protein.

Part of the book: Molecular Docking and Molecular Dynamics