No abstract

No abstract

No abstract

Background Increasing bacterial resistance to quinolones is concerning. Hence, the development of novel quinolones by chemical modifications to overcome quinolone resistance is an attractive perspective in this context. Objective In this study, it is aimed to design and synthesize a novel series of functionalized fluoroquinolones using ciprofloxacin and sarafloxacin cores by hybridization of quinazolinone derivatives. This objective was tested by a comprehensive set of in vitro antibacterial assays in addition to SAR (structure-activity relationship) characterisation studies. Methods A nucleophilic reaction of ciprofloxacin and sarafloxacin with 2-(chloromethyl)quinazolin-4(3H)-one in the presence of NaHCO 3 in dimethylformamide (DMF) was performed to obtain the desired compounds 5a-j. Novel compounds were characterised by 1 H, 13 C-NMR and IR spectroscopy, MS and elemental analysis. In silico pharmacokinetics prediction assays and molecular docking studies were performed to explore the binding characteristics and interactions. Antibacterial activities of the novel compounds were evaluated by Broth microdilution, well diffusion and disc diffusion assays against three gram-positive (Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus and Enterococcus faecalis) and three gramnegative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli). ResultsThe compounds exhibited moderate to good activities against gram-positive bacteria and weak to moderate activities against gram-negative bacteria. Amongst all ciprofloxacin-derivatives, compound 5d was the most potent agent with high antibacterial activity against gram-positive bacteria, including MRSA and S. aureus ((minimum inhibitory concentration (MIC) = 16 nM for both), that is 60 times more potent than ciprofloxacin as parent drug. Compound 5i from sarafloxacinderivatives was the most potent compound against MRSA and S. aureus (MIC = 0.125 μM). Well diffusion and disk diffusion assay results demonstrated confirmatory outcomes for the quantitative broth microdilution assay. Molecular docking study results were in accordance with the results of antibacterial activity assays. ConclusionThe results of the current study demonstrated that the novel ciprofloxacin and sarafloxacin derivatives synthesized here have promising antibacterial activities. Particularly, compounds 5d and 5i have potential for wider antibacterial applications following further analysis.

Dandruff is a common scalp condition causing both a discomfort and an undesired social image. Various studies dating from early 1900s have investigated the condition, but understanding of underlying mechanisms and etiology of the condition is still in its infancy. Formation of dandruff is a common but complex event which has been associated with numerous causal factors. Physiological conditions such as pH, water content, or sebum secretion are some of the host-related factors. An imbalance between these factors can disturb the physiological equilibrium of the scalp that can lead to dandruff formation. However, severity of the condition is strongly related to the lipophilic yeast of the skin microbiota, Malassezia spp. On the other hand, there are recent publications highlighting the role of other scalp microbiota members on dandruff formation. This review investigates the processes leading to the formation of dandruff to provide an etiological description of the condition, with a focus on Malassezia spp.