An Eco-Friendly Method to Synthesize Potent Antimicrobial Tricyclic Flavonoids.

The rapid emergence and spread of multidrug-resistant microorganisms is threatening our ability to treat common infections, with serious medical, social, and economic consequences. Despite substantial progress in the global fight against antibiotic resistance, the number of effective antibiotics is rapidly decreasing, underlying the urgent need to develop novel antimicrobials. In the present study, the green synthesis of novel iodine-substituted tricyclic flavonoids has been accomplished using an eco-friendly reagent, HPW-SiO2, as a cyclization agent for the precursor 3-dithiocarmamic flavanones. In vitro antimicrobial activity of the new compounds was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentrations. All tested compounds displayed potent inhibitory activity against all tested microbial strains, with the lowest MIC values of 0.12 µg/mL and 0.48 µg/mL recorded for compound 5c against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus. Higher MIC values (7.81 µg/mL) were registered for several flavonoids against Gram-negative bacteria Escherichia coli and Acinetobacter pittii. No inhibitory activity was evidenced against Pseudomonas aeruginosa strain. The highest antifungal activity was displayed by flavonoid 5d against Candida krusei (MIC = 3.9 µg/mL). The same compound also exhibited the most potent bactericidal and fungicidal activity against Bacillus subtilis (0.9 µg/mL) and Staphylococcus aureus (1.97 µg/mL), Candida albicans, and Candida krusei (7.81 µg/mL). Based on the reported results, we believe that the novel iodine-substituted tricyclic flavonoids have good potential to become new antimicrobial agents effective against bacterial and fungal strains, including WHO-priority pathogens.

International, prospective cohort study comparing non-absorbable versus absorbable sutures for skin surgery: CANVAS service evaluation.

BACKGROUND: Absorbable or non-absorbable sutures can be used for superficial skin closure following excisional skin surgery. There is no consensus among clinicians nor high-quality evidence supporting the choice of suture. The aim of the present study was to determine current suture use and complications at 30 days after excisional skin surgery. METHODS: An international, prospective service evaluation of adults undergoing excision of skin lesions (benign and malignant) in primary and secondary care was conducted from 1 September 2020 to 15 April 2021. Routine patient data collected by UK and Australasian collaborator networks were uploaded to REDCap©. Choice of suture and risk of complications were modelled using multivariable logistic regression. RESULTS: Some 3494 patients (4066 excisions) were included; 3246 (92.9 per cent) were from the UK and Ireland. Most patients were men (1945, 55.7 per cent), Caucasian (2849, 81.5 per cent) and aged 75-84 years (965, 27.6 per cent). The most common clinical diagnosis was basal cell carcinoma (1712, 42.1 per cent). Dermatologists performed most procedures, with 1803 excisions (44.3 per cent) on 1657 patients (47.4 per cent). Most defects were closed primarily (2856, 81.9 per cent), and there was equipoise in regard to use of absorbable (2127, 57.7 per cent) or non-absorbable (1558, 42.2 per cent) sutures for superficial closure. The most common complications were surgical-site infection (103, 2.9 per cent) and delayed wound healing (77, 2.2 per cent). In multivariable analysis, use of absorbable suture type was associated with increased patient age, geographical location (UK and Ireland), and surgeon specialty (oral and maxillofacial surgery and plastic surgery), but not with complications. CONCLUSION: There was equipoise in suture use, and no association between suture type and complications. Definitive evidence from randomized trials is needed.

Synthetic Flavonoid BrCl-Flav-An Alternative Solution to Combat ESKAPE Pathogens.

ESKAPE pathogens are considered as global threats to human health. The discovery of new molecules for which these pathogens have not yet developed resistance is a high medical priority. Synthetic flavonoids are good candidates for developing new antimicrobials. Therefore, we report here the potent in vitro antibacterial activity of BrCl-flav, a representative of a new class of synthetic tricyclic flavonoids. Minimum inhibitory/bactericidal concentration, time kill and biofilm formation assays were employed to evaluate the antibacterial potential of BrCl-flav. The mechanism of action was investigated using fluorescence and scanning electron microscopy. A checkerboard assay was used to study the effect of the tested compound in combination with antibiotics. Our results showed that BrCl-flav displayed important inhibitory activity against all tested clinical isolates, with MICs ranging between 0.24 and 125 µg/mL. A total kill effect was recorded after only 1 h of exposing Enterococcus faecium cells to BrCl-flav. Additionally, BrCl-flav displayed important biofilm disruption potential against Acinetobacter baumannii. Those effects were induced by membrane integrity damage. BrCl-flav expressed synergistic activity in combination with penicillin against a MRSA strain. Based on the potent antibacterial activity, low cytotoxicity and pro-inflammatory effect, BrCl-flav has good potential for developing new effective drugs against ESKAPE pathogens.

New Insights into the Antimicrobial Potential of Polyalthia longifolia-Antibiofilm Activity and Synergistic Effect in Combination with Penicillin against Staphylococcus aureus.

Widespread antibiotic resistance has led to the urgent need for the identification of new antimicrobials. Plants are considered a valuable potential resource for new effective antimicrobial compounds. Therefore, in the present study, we focused on the antimicrobial activity of Polyalthia longifolia plants harvested from Cameroon using the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assays. The mechanism of action was investigated by employing fluorescence and scanning electron microscopy. The anti-Staphylococcus aureus activity was studied using biofilm inhibition and checkerboard assays. Our results revealed that the tested extracts possess important antimicrobial activities, notably against Gram positive bacteria (MICs as low as 0.039 mg/mL). P. longifolia leaf extracts exhibited a significant bactericidal effect, with a total kill effect recorded after only 2 h of exposure at concentrations equivalent to MBC (0.078 and 0.156 mg/mL). The extracts showed a synergistic antibacterial activity in combination with penicillin against a MRSA clinical isolate and significantly inhibited S. aureus biofilm formation. The mechanism of action is related to the impairment of cell membrane integrity and cell lysis. All these findings suggest that P. longifolia could be an important source of reliable compounds used to develop new antimicrobials.

The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-Candida Activity by Damaging Cell Membrane Integrity.

Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon.