Design and biological evaluation of a novel type of potential multi-targeting antimicrobial sulfanilamide hybrids in combination of pyrimidine and azoles.

This work explored a novel type of potential multi-targeting antimicrobial three-component sulfanilamide hybrids in combination of pyrimidine and azoles. The hybridized target molecules were characterized by 1H NMR, 13C NMR and HRMS spectra. Some of the developed target compounds exerted promising antimicrobial activity in comparison with the reference drugs norfloxacin and fluconazole. Noticeably, sulfanilamide hybrid 5c with pyrimidine and indole could effectively inhibit the growth of E. faecalis with MIC value of 1 µg/mL. The active molecule 5c showed low cell toxicity and did not obviously trigger the development of resistance towards the tested bacteria strains. Mechanism exploration indicated that compound 5c could not only exert efficient membrane permeability, but also intercalate into DNA of resistant E. faecalis to form 5c-DNA supramolecular complex, which might be responsible for its antimicrobial action. The further investigation showed that this molecule could be effectively transported by human serum albumins through hydrogen bonds and van der Waals force.

Review of Properties and Analytical Methods for the Determination of Norfloxacin.

The first-generation quinolones have their greatest potency against Gram-negative bacteria, but newly developed molecules have exhibited increased potency against Gram-positive bacteria, and existing agents are available with additional activity against anaerobic microorganisms. Norfloxacin is a broad-spectrum antimicrobial fluoroquinolone used against Gram-positive and Gram-negative organisms (aerobic organisms). There are different analytical methods available to determine norfloxacin applied in quality control of this medicine in order to ensure its effectiveness and safety. The authors present an overview of the fourth generation of quinolones, followed by the properties, applications, and analytical methods of norfloxacin. These results show several existing analytical techniques that are flexible and broad-based methods of analysis in different matrices. This article focuses on bionalytical and pharmaceutical quality-control applications, such as thin-layer chromatography, microbiological assay, spectrophotometry, capillary electrophoresis (CE), and high-performance liquid chromatography (HPLC).

Quantitative analysis of norfloxacin by 1H NMR and HPLC.

1H NMR and developed previously HPLC methods were applied to quantitative determination of norfloxacin in veterinary solution form for pigeon. Changes in concentration can lead to significant changes in the 1H chemical shifts of non-exchangeable aromatic protons as a result of extensive self-association phenomena. This chemical shift variation of protons was analyzed and applied in the quantitative determination of norfloxacin. The method is simple, rapid, precise and accurate, and can be used for quality control of this drug.

Development and validation of procedures for assessment of competency of non-pharmacists in extemporaneous dispensing.

OBJECTIVES: To develop and validate procedures that may be suitable for assessment of competency of two groups of non-pharmacist staff (pharmacy students and trainee support staff) in extemporaneous dispensing. This is important given the prospect of remote supervision of community pharmacies in the UK. METHODS: Analytical methods were validated according to International Conference on Harmonisation specifications and procedures were optimized to allow efficient drug extraction. This permitted straightforward determination of drug content in extemporaneously prepared lidocaine hydrochloride mouthwashes and norfloxacin creams and suspensions prepared by 10 participants recruited to represent the two groups of non-pharmacist staff. KEY FINDINGS: All 10 participants had completed the extemporaneous dispensing of all three products within 90 min. Extraction and analysis took approximately 15 min for each lidocaine hydrochloride mouthwash and 30 min for each diluted norfloxacin cream and norfloxacin suspension. The mean drug concentrations in lidocaine hydrochloride mouthwashes and diluted norfloxacin creams were within what are generally accepted as being pharmaceutically acceptable limits for drug content (100 +/- 5%) for both groups of participants. There was no significant difference in the mean drug concentration of norfloxacin suspensions prepared by the participant groups. However, it was notable that only one participant prepared a suspension containing a norfloxacin concentration that was within pharmaceutically acceptable limits (101.51%). CONCLUSIONS: A laboratory possessing suitable equipment and appropriately trained staff could cope readily with the large number of products prepared, for example, by a cohort of pre-registration students. Consequently, the validated procedures developed here could usefully be incorporated into the pre-registration examination for pharmacy students and a final qualifying examination for dispensers and pharmacy technicians. We believe that this is essential if the public and the profession are to have confidence in extemporaneous dispensing carried out in the absence of a pharmacist.

A study on the micelle-sensitized Ce(IV)-Na2S2O3-norfloxacin chemiluminescence system and its applications.

A new chemiluminescence (CL) flow-injection method was developed for the determination of norfloxacin. The method is based on the CL reaction of norfloxacin with sodium thiosulphate and Ce(IV) in sulphuric acid medium sensitized by sodium dodecylsulphate. Under optimum conditions, the CL intensity is proportional to the concentration of the norfloxacin in the range 3.89 x 10(-8)-7.18 x 10(-6) g/mL. The detection limit (3 s/k) was 2.21 x 10(-9) g/mL for norfloxacin. The method has been applied successfully to the determination of norfloxacin in pharmaceutical formulations and human urine. The mechanism for this chemiluminescence system is discussed.

Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methyl-3-substituted quinazolin-4-(3H)-ones.

A series of novel 2-methyl-3-substituted quinazolin-4-(3H)-ones have been synthesized by treating (2-methyl-4-oxo-3H-quinazolin-3-yl)dithiocarbamic acid methyl ester with different amines, the starting material dithiocarbamate was synthesized from anthranilic acid. The compounds synthesized were investigated for analgesic, anti-inflammatory and antibacterial activities. All the test compounds exhibited significant activity, the compounds VA2, VA3 and VA4 shown more potent analgesic activity, and the compounds VA3 and VA4 shown more potent anti-inflammatory activity than the reference compound diclofinac sodium.

Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomized study.

The efficacy of a relatively cheap regimen of selective decontamination (SDD) was evaluated in a diverse population of ICU patients. Patients requiring prolonged ICU stay (greater than 5 days) were randomly allocated to a treatment group or control group. Control patients (n = 52) received perioperative antimicrobial prophylaxis and antibiotic treatment was instituted only on sound clinical and bacteriological criteria. Treated patients (n = 48) received gastro-intestinal and oro-pharyngeal decontamination with polymyxin E, norfloxacin, amphotericin B and systemic antibiotic prophylaxis with trimethoprim until decontamination was achieved. The rate of gram-positive infections was not altered by SDD. The incidence of gram-negative respiratory tract, urinary tract and line infections was significantly reduced from 44%, 27% and 15% respectively in the control group to 6%, 4% and 0% in the treatment group. Mortality from nosocomial sepsis and overall mortality were also significantly reduced from 15% and 54% to 0% and 31% respectively. The ICU stay was not reduced by SDD, nor was time on the ventilator or use of therapeutic antibiotics. The reduction in morbidity and mortality was achieved at a relatively low cost.