Quinolone Carboxylic Acid Derivative Research Articles

Revealing Intra- and Intermolecular Interactions Determining Physico-Chemical Features of Selected Quinolone Carboxylic Acid Derivatives.

The intra- and intermolecular interactions of selected quinolone carboxylic acid derivatives were studied in monomers, dimers and crystals. The investigated compounds are well-recognized as medicines or as bases for further studies in drug design. We employed density functional theory (DFT) in its classical formulation to develop gas-phase and solvent reaction field (PCM) models describing geometric, energetic and electronic structure parameters for monomers and dimers. The electronic structure was investigated based on the atoms in molecules (AIM) and natural bond orbital (NBO) theories. Special attention was devoted to the intramolecular hydrogen bonds (HB) present in the investigated compounds. The characterization of energy components was performed using symmetry-adapted perturbation theory (SAPT). Finally, the time-evolution methods of Car–Parrinello molecular dynamics (CPMD) and path integral molecular dynamics (PIMD) were employed to describe the hydrogen bond dynamics as well as the spectroscopic signatures. The vibrational features of the O-H stretching were studied using Fourier transformation of the autocorrelation function of atomic velocity. The inclusion of quantum nuclear effects provided an accurate depiction of the bridged proton delocalization. The CPMD and PIMD simulations were carried out in the gas and crystalline phases. It was found that the polar environment enhances the strength of the intramolecular hydrogen bonds. The SAPT analysis revealed that the dispersive forces are decisive factors in the intermolecular interactions. In the electronic ground state, the proton-transfer phenomena are not favourable. The CPMD results showed generally that the bridged proton is localized at the donor side, with possible proton-sharing events in the solid-phase simulation of stronger hydrogen bridges. However, the PIMD enabled the quantitative estimation of the quantum effects inclusion—the proton position was moved towards the bridge midpoint, but no qualitative changes were detected. It was found that the interatomic distance between the donor and acceptor atoms was shortened and that the bridged proton was strongly delocalized.

Use of Nano Magnetic Zirconia Phosphoric Acid as an Efficient and Recyclable Catalyst for the Clean Synthesis of Some Important Quinolone Carboxylic Acid Derivatives

Use of Nano Magnetic Zirconia Phosphoric Acid as an Efficient and Recyclable Catalyst for the Clean Synthesis of Some Important Quinolone Carboxylic Acid Derivatives

Fast and Green Method to Synthesis of Quinolone Carboxylic Acid Derivatives Using Giant-Ball Nanoporous Isopolyoxomolybdate as Highly Efficient Recyclable Catalyst in Refluxing Water

Various potentials antibacterial fluoroquinolone compounds were prepared by the direct amination of 7-halo-6- fluoroquinolone-3-carboxylic acids with variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b] pyridine using (NH4)42 [MoVI72MoV60O372(CH3COO)30(H2O)72], a Keplerate-type giant-ball nanoporous isopolyoxomolybdate, as a catalyst in refluxing water. The results showed that this catalyst acts as effective catalyst and the reaction proceeded more easily and gave the highest yields of the products in short reaction time under refluxing water. Short reaction times, simple isolation of the products, and usage of eco-friendly catalysts are some features of this procedure. In addition, the catalysts was easily recovered and used in multiple catalytic cycles. This material was prepared according to a previously published literature procedure using inexpensive and readily available starting materials.

Conventional and microwave-assisted synthesis of quinolone carboxylic acid derivatives

Various antibacterial fluoroquinolone compounds are synthesized by the direct amination of 7-halo-6-fluoroquinolone-3-carboxylic acids with a variety of piperazine derivatives and (4aR,7aR)-octahydro-1H-pyrrolo[3,4-b]pyridine using microwave under different reaction conditions. Solvent free high yield microwave synthesis of antibacterial fluoroquinolone compounds is convenient, rapid and environmentally friendly method.

Evaluation of cardiac subacute toxicity of ciprofloxacin in rats using serum biochemical parameters.

Cardiac subacute toxicity induced by ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid, CAS 86393-32-0) a relatively new quinolone carboxylic acid derivative with an extensive antibacterial spectrum was investigated in healthy rats using serum biochemical parameters. Toxicological evaluation was performed in serum samples following the administration of the therapeutic dose regimens of the compound. Cardiac subacute toxicity was evaluated by measuring serum enzyme activity of creatine kinase, creatine kinase isoenzyme-MB (muscular-brain), lactate dehydrogenase and aspartate aminotransferase. The serum biochemical parameters indicated that the cardiac subactue toxicity of ciprofloxacin was: Cipro 1.2 (250 mg) = Cipro 2.4 (500 mg) < Cipro 4.3 (750 mg).

Toxicology of baytril (enrofloxacin)

The prophylactic use of drugs, chemicals and biological substances is necessary to meet the sanitation standards used to maintain high levels of health status. The aim of this article was to present the basic data of the active substance, enrofloxacin, the pharmacokinetics, pharmacodynamics and also the pharmacological safety of this drug.Enrofloxacin as a molecule belonging to the quinolone antimicrobial family is a wide spectrum antibiotic that inhibits DNA gyrase activity in bacterial cells with bactericidal effect. It is at the center of growing attention because of its potential efficacy for the treatment of diseases. This drug is a fluorinated quinolone carboxylic acid derivative, traded as baytril, which has been widely used in veterinary medicine because of its broad spectrum activity. Enrofloxacin has extensively been tested for its safety and it was proven that this medication is rarely toxic in both intravenous and oral routes.Significant side effects occurred only in laboratory animals having a 10 times higherthan the recommended dose. The active substance is not teratogenic or mutagenic and in most scientific findings, there is no evidence of a potential risk to applicators andconsumers. As a conclusion it can be used in different administration routes in farm animals against a wide range of microorganism but it is important to say that enrofloxacin has not been shown to be safe for use in poultry as Campylobacterinfections resistant to fluoroquinolones has increased significantly since the use of enrofloxacin in poultry was approved. Key words: Enrofloxacin, spectrum, safety, teratogenic, mutagenic.

English

The prophylactic use of drugs, chemicals and biological substances are necessary to meet the sanitation standards used to maintain high levels of health status. The aim of this article was to present the basic data of the active substance of enrofloxacin, the pharmacokinetics, pharmacodynamics and also the pharmacological safety of this drug. Enrofloxacin as a molecule belongs to the quinolone antimicrobial family, and it is a wide spectrum antibiotic that inhibits DNA gyrase activity in bacterial cells with bactericidal effect. It is at the center of growing attention because of its potential efficacy for the treatment of diseases. This drug is a fluorinated quinolone carboxylic acid derivative, traded as baytril, which has been widely used in veterinary medicine because of its broad spectrum activity. Enrofloxacin has extensively been tested for its safety and it was proven that this medication is rarely toxic in both intravenous and oral routes. Significant side effects occurred only in laboratory animals having a 10 times higher than the recommended dose. The active substance is not teratogenic or mutagenic and in most scientific findings, there is no evidence of a potential risk to applicators and consumers. As a conclusion, it can be used in different administration routes in farm animals against a wide range of microorganism. Also, enrofloxacin is not safe to be use in poultry as Campylobacter infections have increased significantly since the use of enrofloxacin in poultry because of the resistance of such organism to fluoroquinolone groups.

Ciprofloxacin enhances T cell function by modulating interleukin activities

Ciprofloxacin (CIP) is a quinolone carboxylic acid derivative with a broad spectrum of antibacterial activity. CIP (0.1-30 micrograms/ml) enhanced DNA synthesis of mouse spleen cells and human peripheral blood lymphocytes (PBL) that had been activated with T cell mitogens or with alloantigens. In addition, CIP increased the amount of IL-2 found in the supernatants of phytohaemagglutinin (PHA)-stimulated human PBL. The presence of CIP in the medium (0.3-10 micrograms/ml) increased the levels of IL-1 found in the culture supernatants of adherence-enriched mouse macrophages, human monocyte/macrophages and a human monocytic cell line stimulated with lipopolysaccharide. In contrast there was no effect of CIP on the release of IL-1 by freshly isolated human monocytes or by cells of the keratinocyte line, A431. CIP alone had no influence on the basal release of IL-2 by NOB-1 cells, a T cell line that responds to IL-1 with an increase in IL-2 synthesis, but, in combination with recombinant IL-1, CIP significantly enhanced the release of IL-2 by these cells. The results of this study suggest that CIP modulates the immune response at two levels--the production of IL-2 by activated T cells and the production of IL-1 by activated monocyte/macrophages. However, CIP did not affect the primary antibody response in vitro or in vivo against sheep erythrocytes and ovalbumin respectively. Thus the enhancing action of ciprofloxacin on the immune system appears to be restricted to T cell function and macrophage/T cell interactions.

The effect of some excipients on the formulation of norfloxacin 400mg tablets

Norfloxacin a synthetic, broad-spectrum quinolone carboxylic acid derivative, active against Gram negative &amp; Gram-positive bacteria. Used clinically in the treatment of acute and chronic urinary tract infections, cystitis ,urethritis, pyelonephritis, prostatitis&amp; gastroenteritis . This study is concerned with the formulation of 400mg Norfloxacin coated tablets with 710mg weight, 12mm in diameter, less than 10minutes disintegration time, &amp; less than 1 % friability. Many trials were made to prepare a satisfactory tablet formula for the drug by using wet-granulation method with various additives. It was found that Polyvinylpyrrolidone as a binder gives the most satisfactory tablets. The effect of disintegrants on drug release was also investigated on the selected formulas. Conventional corn starch, sodium starch glycolate and microcrystalline cellulose were tried as disintegrants. It was found that cross-caramellose (carboxymethylcellulose) was the best disintegrants. A comparative study on the physical properties of the prepared tablets with Noroxacine ( Razi labs,Aleppo.Syria ) , Neofloxacin ( the Alexandria. Egypt ), and Norfloxacin showed that the release of the drug from the selected formula was similar to that obtained from Alexandria. The stability of the prepared tablets was studied at 25°C, 40°C, 50°C, &amp;70°C and the expiration date was calculated and found to be equal to 7.3 years, 4.7 years, and 2.4 years &amp; four months respectively. Key word: Norfloxacin- Pharmacokinetics.Fluoroquinolone- Norfloxacin formulation.

Europium(III) and terbium(III) chelates of quinolonecarboxylic acid derivatives as labels for immunofluorimetric assay

Luminescence properties of Tb(III) and Eu(III) complexes of quinolonecarboxylic acid derivatives were studied. Optimal conditions of luminescence were determined, and the influence of surfactants and diethylenetriaminepentaacetic acid on the luminescence properties of the complexes was studied. It was demonstrated that species-specific immunoglobulins labeled with terbium ions can be determined with the detection limit of the lanthanide label 5 x 10-14 M.

A comparative study of the antibacterial activity of dioxydin, quinolone-carboxylic acid derivatives, and quiditene under aerobic and anaerobic conditions

A comparative study of the antibacterial activity of dioxydin, quinolone-carboxylic acid derivatives, and quiditene under aerobic and anaerobic conditions

Effects of quinolone carboxylic acid derivatives on GABA A receptor-mediated stimulation of gastric acid secretion and intestinal motility

The present study investigates the effects of some quinolone carboxylic acid derivatives on GABA A receptor-mediated excitatory responses in gastrointestinal preparations in vivo and in vitro. In stomach-perfused rats, norfloxacin, nalidixic and pipemidic acid dose dependently antagonized acid hypersecretion induced by muscimol. Under the same conditions, the quinolone derivatives failed to modify acid hypersecretion evoked by 2-deoxy-D-glucose. In the isolated guinea-pig ileum, norfloxacin, nalidixic and pipemidic acid antagonized muscimol-elicited contractions in a non-competitive manner. In contrast, these drugs did not influence ileal cholinergic contractions evoked by transmural electrical stimulation or by exogenous acctylcholine. Taken together, these results suggest that the quinolone derivatives tested act as antagonists at both central and peripheral GABA A receptors. In addition, GABA A-mediated gastrointestinal responses might represent a simple and reliable method to assay the GABA A receptor antagonist properties of new quinolone derivatives.

Transport of the new quinolone antibacterial agents of lomefloxacin and ofloxacin by rat erythrocytes, and its relation to the nicotinic acid transport system.

Transport mechanism of quinolonecarboxylic acid derivatives (quinolones), lomefloxacin and ofloxacin, in rat erythrocytes was investigated. The uptake of lomefloxacin by erythrocytes was apparently nonsaturable over the concentration range of 0.1-1.0 mM at 27 degrees C and pH 7.4. In the case of ofloxacin, however, the erythrocytes took up ofloxacin in a concentration dependent manner at 20 degrees C and pH 7.4, with a maximum rate (Jmax) of 28.8 +/- 0.98 pmol/10(6) cells/s and a Michaelis constant (Kt) of 0.92 +/- 0.15 mM. An increase in the medium osmolarity caused a decrease in the [14C]lomefloxacin uptake, indicating that the drug is transported into the intracellular space of erythrocytes. The uptake of [14C]lomefloxacin by the erythrocytes was independent of pH but increased above pH 6.0, and, moreover, was dependent on temperature with an activation energy of 16.6 kcal/mol. The uptake of [14C]lomefloxacin was competitively inhibited by a water-soluble vitamin, nicotinic acid, with an inhibition constant (Ki) of 16.1 mM, but not inhibited by 10 mM of L-alanine, glucose, p-aminohippuric acid (PAH), N-methyl-nicotinamide (NMN) or tetraethylammonium chloride (TEA). These lines of evidence suggest that the transport system of lomefloxacin and ofloxacin in rat erythrocytes is common with that of a water-soluble vitamin, nicotinic acid, to which quinolones are structurally analogous.

Quinolonecarboxylic acid derivatives as GABA-A receptor antagonists

The present study investigates the effects of some quinolone carboxylic acid derivatives on GABAA receptor-mediated excitatory responses in gastrointestinal preparations in vivo and in vitro. In stomach-perfused rats, norfloxacin, nalidixic and pipemidic acid dose dependently antagonized acid hypersecretion induced by muscimol. Under the same conditions, the quinolone derivatives failed to modify acid hypersecretion evoked by 2-deoxy-D-glucose. In the isolated guinea-pig ileum, norfloxacin, nalidixic and pipemidic acid antagonized muscimol-elicited contractions in a non-competitive manner. In contrast, these drugs did not influence ileal cholinergic contractions evoked by transmural electrical stimulation or by exogenous acctylcholine. Taken together, these results suggest that the quinolone derivatives tested act as antagonists at both central and peripheral GABAA receptors. In addition, GABAA-mediated gastrointestinal responses might represent a simple and reliable method to assay the GABAA receptor antagonist properties of new quinolone derivatives.

Inhibitory effects of quinolone antibacterial agents on gamma-aminobutyric acid binding to receptor sites in rat brain membranes.

The specific binding of 3H-labeled gamma-aminobutyric acid ([3H]GABA) to synaptic plasma membranes from rat brains was inhibited by various quinolonecarboxylic acid derivatives (quinolones), and these inhibitions were concentration dependent. The binding of [3H]muscimol to GABAA sites was also inhibited. These inhibitory potencies differed widely among the quinolones examined. The Dixon plots showed that a newly developed difluorinated quinolone, NY-198 [1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3- quinolinecarboxylic acid hydrochloride], competitively inhibits the receptor bindings of [3H]GABA and [3H]muscimol. In conclusion, our findings suggest that the inhibition of GABA binding to receptors (including uptake sites) in the brain may be involved in the induction of epileptogenic neurotoxicities by quinolones.

Entry of the new quinolone antibacterial agents of ofloxacin and NY-198 into the central nervous system in rats.

The present study describes quantitatively the pharmacokinetics of the antibacterial agents, ofloxacin and NY-198 (quinolonecarboxylic acid derivatives), in the central nervous system in rats by physiological modeling of the penetration, distribution and sequestration processes. The stimulation curves corresponded well with the observed concentrations in the cerebrospinal fluid (CSF) and various brain regions after intravenous bolus administration. The estimated cerebrovascular diffusion clearances were considerably small compared with reported serum flow rates and similar among the brain parenchymal tissues examined. The distribution volume of each drug in each brain region was almost the same as the brain extracellular space (15 to 25% of the wet weight). It was also found that the Kp values of these drugs were similar among the various brain regions. These lines of evidence suggest that the antibacterial agents, ofloxacin and NY-198, localized only in the brain extracellular space and exhibited little region-specificity in distribution into the brain. Moreover, it was suggested from unexpectedly low CSF: serum concentration ratios after intravenous administration that these quinolones, which once diffused into CSF, could be sequestrated from CSF to blood via some transport system.

Susceptibility of bacteria isolated from the patients with lower respiratory tract infections to antibiotics (1985)

It has been more than 4 years since third-generation cephems were introduced into clinical practice. The range of our drug selection definitely tends to increase, because we today have more antibiotics with wider spectrum, antibiotics with strong activities only against Gram-negative strains, such as monobactams, and those with tremendously high activities such as quinolone carboxylic acid derivatives, in comparison to those we had in the past. Among isolates obtained mainly from sputa of 567 patients with lower respiratory tract infections at 16 institutions throughout Japan between September of 1985 and March of 1986, 741 strains were determined to be causative organisms. MIC's of various antimicrobial agents were determined against 67 strains of Staphylococcus aureus, 100 strains of Streptococcus pneumoniae, 199 strains of Haemophilus influenzae, 92 strains of non-mucoid Pseudomonas aeruginosa, 40 strains of mucoid P. aeruginosa, 29 strains of Klebsiella pneumoniae, 10 strains of Escherichia coli and for 42 strains of Branhamella catarrhalis out of the above 741 strains to determine their drug sensitivities. As for types of lower respiratory tract infections found in 1981--1983, 57.9--64.5% of the infections were chronic respiratory infections; i.e., chronic bronchitis, chronic bronchiolitis and bronchiectasis. These chronic infections, including diffuse panbronchiolitis (DPB), were found in 63.1% of lower respiratory tract infections in 1984. Their incidence dropped to 54.0% in 1985, even though DPB was included; i.e., the incidence of chronic bronchiolitis was 5.5%, that of DPB was 7.1%, and that of bronchial asthma associated with lower respiratory tract infections in 1985 was 8.8% which was twice as much as that found in 1981--1984. Although bacterial pneumonia was found in 24.8% of all the cases in 1981, its incidence was reduced to 11.0% in 1983, 15.1% in 1984, and 17.6% in 1985. This reduction seemed to have resulted from gradual decreases in the occurrence of bacterial pneumonia among the young population. As with usual years, a high incidence rate in a total lower respiratory tract infections in 1985 was found among older patients; namely, 73.5% was at the age of 50 or over (417/567). Next, we determined relationships between clinical isolates and isolates from respiratory infections, including chronic bronchitis, chronic bronchiolitis, bronchiectasis and DPB. H. influenzae was isolated from 50.5% of patients with these infections in 1981; however, the detection rate decreased by about 20% to 29.7% in 1985. P. aeruginosa was consistently isolated, between 24.1% and 30.4% every year.(ABSTRACT TRUNCATED AT 400 WORDS)

Penetration of ciprofloxacin into kidney, fat, muscle and skin tissue.

Ciprofloxacin is a new quinolone carboxylic acid derivative with antibacterial activity against a broad spectrum of gram-positive and gram-negative bacteria causing nosocomial urinary tract infections. It can be given by either the oral or the parenteral route (1). The purpose of this study was to evaluate the serum and tissue pharmacokinetics of ciprofloxacin after i.v. administration at various times prior to urological surgery.

Penetration of ciprofloxacin into female pelvic tissues.

Ciprofloxacin (Bay 0 09867) is a new quinolone carboxylic acid derivative which has a broad spectrum of antibacterial activity and is highly active against both gram-negative and gram-positive organisms (1). The high volume of distribution of ciprofloxacin (2 1/kg) suggests that it is distributed in both the intravascular and extravascular spaces (2).

Ciprofloxacin, a quinolone carboxylic acid compound active against aerobic and anaerobic bacteria.

The in vitro activity of ciprofloxacin, a quinolone-carboxylic acid derivative, was compared with those of norfloxacin, cefotaxime, cephalexin, ceftazidime, moxalactam, amoxicillin, and methicillin and other agents, as appropriate. The MICs of ciprofloxacin for 90% of members of the family Enterobacteriaceae and for Pseudomonas aeruginosa, Neisseria spp., and Bacteroides fragilis were between 0.005 and 0.8 micrograms/ml, whereas streptococci and staphylococci were all inhibited by less than or equal to 6.3 micrograms/ml. Ciprofloxacin was 4- to 32-fold more active than norfloxacin and inhibited gentamicin-, ameikacin-, cefotaxime-, and moxalactam-resistant members of the family Enterobacteriaceae and P. aeruginosa and methicillin-resistant Staphylococcus aureus. The activity of ciprofloxacin was not affected by serum but decreased in the presence of acid urine. The frequency of resistance to ciprofloxacin was between 10(-7) and 10(-9).