Novel fluoroquinolones analogues bearing 4-(arylcarbamoyl)benzyl: design, synthesis, and antibacterial evaluation.

Bacterial resistance to fluoroquinolone has been increasing at an alarming rate worldwide. In an attempt to find more potent anti-bacterial agents, an efficient, straightforward protocol was performed to obtain a large substrate scope of novel ciprofloxacin and sarafloxacin analogues conjugated with 4-(arylcarbamoyl)benzyl 7a-ab. All prepared compounds were evaluated for their anti-bacterial activities against three gram-positive strains (Methicillin resistant staphylococcus aureus (MRSA), Staphylococcus aureus, and Enterococcus faecalis) as well as three gram-negative strains (Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli) through three standard methods including broth microdilution, agar-disc diffusion, and agar-well diffusion assays. Most of the compounds exhibited great to excellent anti-bacterial potencies against MRSA and S. aureus. Among the targeted compounds, derivative 7n exhibited great antibacterial potency, which was noticeably more potent than parent ciprofloxacin. Subsequently, a molecular docking study was performed for this compound to find out its probable binding mode with the active site of S. aureus DNA gyrase (PDB ID: 2XCT).

Meropenem in combination with baicalein exhibits synergism against extensively drug resistant and pan-drug-resistant Acinetobacter baumannii clinical isolates in vitro.

Several studies have demonstrated that the effectiveness of carbapenems against drug-resistant Acinetobacter baumannii infections has been decreasing. Combination therapy with two or more drugs is currently under investigation to overcome the emerging resistance against carbapenems. In this study, we tested the possible synergistic interactions of a potent antibacterial flavonoid, baicalein, with meropenem to illustrate this duo's antibacterial and antibiofilm effects on 15 extensively drug resistant or pan-drug-resistant (XDR/PDR) A. baumannii clinical isolates in vitro. Isolates included in the study were identified with MALDI-TOF MS, and antibiotic resistance patterns were studied according to EUCAST protocols. Carbapenem resistance was confirmed with the modified Hodge test, and resistance genes were also analyzed with genotypical methods. Then, checkerboard and time-kill assays were performed to analyze antibacterial synergism. Additionally, a biofilm inhibition assay was performed for screening the antibiofilm activity. To provide structural and mechanistic insights into baicalein action, protein-ligand docking, and interaction profiling calculations were conducted. Our study shed light on the remarkable potential of the baicalein-meropenem combination, since either synergistic or additive antibacterial activity was observed against every XDR/PDR A. baumannii strain in question. Furthermore, the baicalein-meropenem combination displayed significantly better antibiofilm activity in contrast to standalone use. In silico studies predicted that these positive effects arose from inhibition by baicalein of A. baumannii beta-lactamases and/or penicillin-binding proteins. Overall, our findings highlight the prospective potential benefits of baicalein in combination with meropenem for the treatment of carbapenem-resistant A. baumannii infections.

Monitoring of microbiological dynamics in beach sand and seawater samples from recreational and non-recreational beaches over a two-year period.

The frequencies of Escherichia coli, Staphylococcus aureus and Methicillin-resistant S. aureus (MRSA) and 'aerobic mesophilic bacteria' (AMB) counts in different seasons and marine sources were compared to understand the microbiological dynamics at beaches in N. Cyprus. Also, antibiotic resistance patterns were evaluated. The characterization and AMB enumeration studies were performed by conventional microbiological methods. AMB counts increased from winter to summer significantly (45.5*104 CFU/mL to 2.5*106 CFU/mL). Similarly, percentage detection frequencies of the bacteria were higher in summer compared to winter and were significant particularly for E. coli in both sand and seawater samples in 2019 and 2020 (p = 0.0181, p = 0.0142, p = 0.1257, p = 0.0446, respectively). However, a significant difference was not detected in percentage detection frequencies in terms of different sources or recreational status of beaches. The highest resistance percentages were detected against beta-lactam and lincosamides group of antibiotics. Results of the study signified that regular microbiological monitoring for beaches is essential.

Synergistic Combination of Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid and Natural Flavonoid Curcumin Exhibits Anticancer and Antibacterial Activity.

BACKGROUND AND OBJECTIVE: Curcumin is an effective anti-cancer agent used in thyroid cancer treatments. However, its use in clinical applications is limited due to low solubility and bioavailability. In this study, a novel combination strategy was applied by combining curcumin with Suberoylanilide Hydroxamic Acid (SAHA) to increase both bioavailability of curcumin and the efficiency of SAHA, which have limited efficiency when used alone. METHODS: MTT assay was used to determine the cell viability of B-CPAP cells upon treatment with SAHA, curcumin and their combinations. Synergistic interactions between two agents were analyzed by Calcusyn software. Apoptosis and cell cycle assays were measured by flow cytometry. Expressions of apoptotic and cell cyclerelated proteins (PARP, P21/CDKN1A/WAF1, P27/KIP1) were examined by western blot analysis. Broth microdilution assay was performed to determine Minimum Inhibitory Concentration (MIC) values against S. aureus. RESULTS: Based on MTT assay, IC50 values for SAHA and curcumin were determined as 0.91µM and 20.97µM, respectively. The combination index CI value was determined as 0.891 in B-CPAP cells, which demonstrate synergistic activity. The apoptotic effect was achieved by combination treatment (51.85%) on B-CPAP cells using half of the dose required for SAHA and curcumin alone. Combination treatment showed a significant increase in the percentage of B-CPAP cells in the S-phase due to cell arrest. Cleaved-PARP, P21/CDKN1A/ WAF1 and P27/KIP1 protein expressions were upregulated. Curcumin was found to have better anti-microbial activity than SAHA as having a lower MIC value, and checkerboard synergy analysis revealed that the two compounds co-operate synergistically for the in vitro killing of S. aureus. CONCLUSION: In the present study, synergistic combinations of SAHA and curcumin were shown to have both anti-cancer and antibacterial activities that would provide a novel thyroid cancer treatment strategy.

Design, synthesis, molecular docking study, and antibacterial evaluation of some new fluoroquinolone analogues bearing a quinazolinone moiety.

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 NaHCO3 in dimethylformamide (DMF) was performed to obtain the desired compounds 5a-j. Novel compounds were characterised by 1H, 13C- 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 gram-negative bacteria (Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli). RESULTS: The 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 sarafloxacin-derivatives 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. CONCLUSION: The 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.

Fabrication of a novel nontoxic trichlorophenol-epichlorohydrin-based compound with high antimicrobial activity and thermal stability.

The aim of this study was to modify a discontinued, toxic antiseptic agent 2,4,5-trichlorophenol (TCP) by reacting it with epichlorohydrin (ECH) to obtain a nontoxic novel compound with similar antimicrobial effectiveness. A novel compound named {[1,3-bis(2,4,5-trichlorophenoxy) propan-2-yl] oxy}-3-(2,4,5-trichlorophenoxy) hexan-2-ol (TPTH) was synthesized from this reaction. Chemical and physical structures of the product were characterized by FTIR, MS, Uv-vis, NMR, SEM and TEM. The thermal stability of TPTH was evaluated by conducting thermogravimetric analysis. Biological interactions of the compound were investigated by performing antimicrobial activity and cytotoxicity assays. The compound displayed a good antimicrobial activity where minimum inhibitor concentrations were found to be 0.02, 0.08, and 0.15 µg mL-1 against Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) respectively. Additionally, well diffusion assay demonstrated that, the zone of inhibitions for S. aureus, MRSA and E. coli were 24 mm, 22 mm and 18 mm, respectively. Cytotoxicity assay results revealed that TPTH is nontoxic against cells at effective anti-microbial concentrations. TPTH shows thermal stability up to 220 °C. Results here demonstrate the successful conversion of toxic TCP to a nontoxic form; TPTH with a good anti-microbial activity and thermal stability.

An overview of Leishmaniasis with a focus on the island of Cyprus.

Leishmaniasis is a parasitic disease of tropics, subtropics, and southern Europe which is classified as a neglected tropical disease. There is a paucity of knowledge for this disease especially in some parts of the world where leishmaniasis is endemic such as Cyprus island in the Mediterranean. This narrative review revealed cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) as the dominant type of human leishmaniasis in the island. Host and disease type identification studies based on cats, dogs and rats showed Leishmania infantum parasite to be the leading species among others with a seroprevalence rate ranging from 3.55% to 14.9% in selected hosts with an indication of dogs as the main animal reservoir. Lack of focus on potential wild animal hosts creates an important evidence gap to overcome for the purpose of controlling leishmaniasis. We aim to present asynoptical review of leishmaniasis to critically analyse currently available data in literature about this disease in Cyprus.

Combined effects of quercetin and curcumin on anti-inflammatory and antimicrobial parameters in vitro.

In this in-vitro study, combinatory anti-inflammatory interactions between Quercetin (Q) and Curcumin (C) along with their combined antimicrobial activity against MRSA were studied. Anti-inflammatory markers of (i) COX-2 expression, (ii) NFκß activation and (iii) NO levels were investigated. Antimicrobial synergy was tested by checkerboard assay. We found that, treatment with the "low-concentration combination group" (QC), where Q and C were combined, resulted in significant downregulation of COX-2 expression (P < 0.0001) and inhibition of NFκß activation in cells (P < 0.0001), to a similar extent to that induced by higher concentrations of Q and C alone. QC treatment was also found to induce a significant reduction in NO production (P < 0.0001). QC was significantly more effective in the reduction of total NO levels when compared to Q alone (P < 0.001). Checkerboard assay indicated that the combination of Q and C provides better killing of MRSA in lower dilutions than standalone Minimum Inhibitory Concentrations. These results suggest that combining low concentrations of Q and C yield similar or better anti-inflammatory effectiveness when compared to treatment with each agent alone. Moreover, they co-operate synergistically in the context of antimicrobial activity, with an increased effectiveness when compared to Q or C alone at high concentrations.

Putting It All Together to Understand the Role of Malassezia spp. in Dandruff Etiology.

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.

Clinical and Laboratory Features of Six Cases of Candida and Dermatophyte Folliculitis and a Review of Published Studies.

Although some studies have investigated the epidemiological characteristics of Malassezia folliculitis (MF), little is known about the clinical features and laboratory characteristics of folliculitis caused by other fungi. In this prospective study, 158 patients with folliculitis were identified, and cytological and mycological examinations were performed. The positive fungal cultures were confirmed using conventional methods, ITS sequencing and HWP1 analysis. Additionally, an in vitro antifungal susceptibility test was performed. Of 158 patients with folliculitis, 65 (41.1 %) were found to have fungal folliculitis. The most common (90.8 %) fungal folliculitis was MF. Non-MF fungal folliculitis was detected in 6 (9.2 %) patients. Four patients were diagnosed with dermatophytic folliculitis (Trichophyton rubrum in three patients and Arthroderma vanbreuseghemii in one patient), and two patients were diagnosed with Candida albicans folliculitis. Although only 5 of the 6 samples were found to be positive via a potassium hydroxide test, all May-Grünwald-Giemsa-stained samples were positive. Both of the C. albicans isolates demonstrated a susceptibility profile to itraconazole, and all four dermatophytes were susceptible to terbinafine. All six patients completely recovered with systemic and topical treatment. This study revealed that dermatophytes and C. albicans are the primary causative agents of non-Malassezia fungal folliculitis. We compared our findings with published reports on fungal folliculitis.

Epidemiological characteristics of Malassezia folliculitis and use of the May-Grünwald-Giemsa stain to diagnose the infection.

Various bacterial, fungal, parasitic, and viral pathogens can cause folliculitis, which is often mistakenly treated with antibiotics for months or even years. A laboratory diagnosis is required before therapy can be planned. Here, we describe the prevalence and risk factors, as well as the clinical, cytological, and mycological characteristics, of patients with Malassezia folliculitis (MF) in Adana, Turkey. We also report the treatment responses of the MF patients and describe the Malassezia spp. using culture-based molecular methods. Cytological examinations were performed in 264 folliculitis patients, 49 of whom (18.5%) were diagnosed with MF. The positivity of the May-Grünwald-Giemsa (MGG) smear was higher (100%) than that of the potassium hydroxide test (81.6%). Using Wood's light, yellow-green fluorescence was observed in 66.7% of the MF patients. Identification using the rDNA internal transcribed spacer region revealed that Malassezia globosa was the most common species, followed by Malassezia sympodialis, Malassezia restricta, and Malassezia furfur. The MF patients were treated with itraconazole capsules (200 mg/d) for 2 weeks. Complete recovery was observed in 79.6% of the patients. These novel findings help improve our current understanding of the epidemiological characteristics of MF and establish MGG as a practical tool for the diagnosis of MF.