Minimum Fungicidal Concentration Research Articles

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis.

Fluconazole (FNL) is one of the first-line treatments for fungal keratitis as it is an effective broad-spectrum antimicrobial commonly administered orally or topically. However, FNL has a very low water solubility, limiting its drug formulation, therapeutic application, and bioavailability through tissues. To overcome these limitations, this study aimed to develop FNL inclusion complexes (FNL-IC) with cyclodextrin (α-cyclodextrin, sulfobutylether-β-cyclodextrin, and hydroxypropyl-γ cyclodextrin) and incorporate it into a dissolvable microneedle (DMN) system to improve solubility and drug penetration. FNL-IC was evaluated for saturation solubility, Fourier transform infrared spectroscopy, differential scanning calorimetry, in vitro release, minimum inhibitory concentration, minimum fungicidal concentration, and time-killing assay. DMN-FNL-IC was evaluated for mechanical and insertion properties, surface pH, moisture absorption ability, water vapor transmission, and drug content recovery. Moreover, ocular kinetic, ex vivo antimicrobial, in vivo antifungal, and chorioallantoic membrane (HET-CAM) assays were conducted to assess the overall performance of the formulation. Mechanical strength and insertion properties revealed that DMN-FNL-IC has great mechanical and insertion properties. The in vitro release of FNL-IC was significantly improved, exhibiting a 9-fold increase compared to pure FNL. The ex vivo antifungal activity showed significant inhibition of Candida albicans from 6.54 to 0.73 log cfu/mL or 100-0.94%. In vivo numbers of colonies of 0.87 ± 0.13 log cfu/mL (F2), 4.76 ± 0.26 log cfu/mL (FNL eye drops), 3.89 ± 0.24 log cfu/mL (FNL ointments), and 8.04 ± 0.58 log cfu/mL (control) showed the effectiveness of DMN preparations against other standard commercial preparations. The HET-CAM assay showed that DMN-FNL-IC (F2) did not show any vascular damage. Finally, a combination of FNL-IC and DMN was developed appropriately for ocular delivery of FNL, which was safe and increased the effectiveness of treatments for fungal keratitis.

Development of treatment strategies by comparing the minimum inhibitory concentrations and minimum fungicidal concentrations of azole drugs in dermatophytes.

We compared the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of azoles in antifungal drug-susceptible, terbinafine-resistant, and lowly itraconazole (ITCZ)-susceptible strains of dermatophytes. To assess the MICs of ITCZ, ravuconazole (RVCZ), efinaconazole (EFCZ), and luliconazole (LUCZ) in the isolates, broth microdilution assays were performed based on the Clinical and Laboratory Standards Institute M38-A2 guidelines with modifications. After the assays for determining the MICs, the inoculum suspensions in wells were resuspended, then 10 μL of the growth solution in each well was inoculated onto potato dextrose agar with the use of a pipette. After 7 days of incubation at 28°C, the MFCs were determined as the lowest concentration of a drug that allowed the growth of colonies on the potato dextrose agar. The MICs in the dermatophytes were <0.03 to >32 mg/L for ITCZ, <0.03 to 4 mg/L for RVCZ, <0.03 to 2 mg/L for EFCZ, and <0.03 mg/L for LUCZ. The MFCs in the dermatophytes were 1 to >32 mg/L for ITCZ, 0.06 to >32 mg/L for RVCZ, <0.03 to 4 mg/L for EFCZ, and <0.03 to 2 mg/L for LUCZ. If the drug susceptibility test shows that the fungi are resistant to the drug, the treatment can be changed to a susceptible drug in advance, or if the fungi are low-susceptible, the treatment can be done with the recognition that it may require a longer treatment period than usual.

Hytochemical Analysis and Determination of MIC and MFC of Cacao Leaves Extract (Theobroma cacao L.) against Malassezia furfur

Pityriasis versicolor is a disease caused by Malassezia furfur. One of the plants that can potentially act as antifungal is cacao leaves (Theobroma cacao L.), which contain several secondary metabolite compounds, including alkaloids, flavonoids, tannins, quinones, terpenoids, and saponins. This study aims to determine the phytochemical analysis and the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) of cacao leaves ethanolic extract against M. furfur. Extracts were obtained by maceration using 70% ethanol and phytochemicals analysis using Herborne’s method. Furthermore, the extracts were made into concentrations’ variations of 3.125%; 6.25%; 12.5%; 25%; 50%; and 100% for testing antifungal activity, with 10% DMSO as negative control and 2% Ketoconazole and Itraconazole as positive controls. MIC was performed with liquid macrodilution method, and MFC was performed with spread method. The results of phytochemical analysis showed that the extract contained alkaloids, flavonoids, phenols, tannins, quinones, terpenoids and saponins. MIC value was obtained at concentration of 50% and MFC value was obtained at 100%. Cacao leaves ethanolic extract with concentration of 50% can inhibit M. furfur’s growth and with 100% can eliminate M. furfur.

Antifungal Activity, Mode of Action, and Cytotoxicity of 4-chlorobenzyl p-coumarate: a Promising New Molecule.

Fungal infections represent a serious health problem worldwide. The study evaluated the antifungal activity of 4-chlorobenzyl p-coumarate, an unprecedented semi-synthetic molecule. Docking molecular and assay experiments were conducted to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC), mode of action, effect on growth, fungal death kinetics, drug association, effects on biofilm, micromorphology, and against human keratinocytes. The investigation included 16 strains ofCandidaspp, includingC. albicans,C. krusei,C. glabrata,C. tropicalis,C. dubliniensis,C. lusitaniae,C. utilis,C. rugosa,C. guilhermondi, andC. parapsilosis. Docking analysis predicted affinity between the molecule and all tested targets. MIC and MFC values ranged from 3.9 µg/mL (13.54 µM) to 62.5 µg/mL (217.01 µM), indicating a probable effect on the plasma membrane. The molecule inhibited growth from the first hour of testing. Association with nystatin proved to be indifferent. All concentrations of the molecule reduced fungal biofilm. The compound altered fungal micromorphology. The tested compound exhibited an IC50 of 7.90 ± 0.40 µg/mL (27.45 ± 1.42 µM) for keratinocytes. 4-chlorobenzyl p-coumarate showed strong fungicidal effects, likely through its action on the plasma membrane and alteration of fungal micromorphology, and mildly cytotoxic to human keratinocytes.

ANTIBACTERIAL AND ANTIFUNGAL ACTIVITIES OF SOME HYDRAZONES SYNTHESIZED FROM NICOTINIC ACID HYDRAZIDE

N’-(2-pyridinylmethylene)nicotinohydrazide A, N’-(4-pyridinylmethylene)nicotinohydrazide B, N’-(2- ethoxybenzylidene)nicotinohydrazide C, N’-(4- ethoxybenzyldene)nicotinohydrazide D and N’-(2-hydroxyl-5-methoxybenzylidene)nicotinohydrazide E, was prepared by refluxing the ethanolic solution of nictonic acid hydrazide and ethanolic solutions of 2-pyridinrcarboxaldehyde, 4-pyridinecarboxaldehyde, 2-ethoxybenzaldehyde, 4-ethoxybenzaldehyde and 2-hydroxy-5-methoxybenzaldehyde in 1:1 mole ratio for 4 hours in a separate reactions. The compounds obtained had a melting point between (120-236 oC) and a percentage yield between (52.38-77.70 %). They were crystalline solids. The compounds' solubility were assessed in water, ethanol, methanol, acetone, hexane, diethyl ether, dimethyl sulfoxide (DMSO), ethyl acetate, and chloroform. The substances were discovered to be fully soluble in DMSO and methanol. FT-IR, 1H-NMR and 13C-NMR were used for the characterization of the compounds. The antibacterial and antifungal properties were tested against Methicillin-resistant Staphylococcus Aureus, Vancomycin-resistant Enterococci, S. aureus, S. typhi, P. aeruginosa, A. nigre, A. flavus, and C. albicans. The zones of inhibitions ranged from 22 to 28 mm and the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC) were found to be 0.063 mg/mL, 0.125 mg/mL and 0.125 mg/mL respectively. These indicated that the compounds might be good potential drug candidates.

Total Phenolic Compound and Antimicrobial Activity of Spirogyra spp.

Spirogyra spp. is widely distributed in freshwater habitats and is included in the category of natural resources whose significance and advantages have been researched. In this study, 6 samples of Spirogyra spp. were collected: Spirogyra ellipsospora Transeua from Bueng Kan province, Spirogyra sp.1 from Sakon Nakhon Province and S. neglecta (Hassall) Kützing, S. ellipsospora Transeua, Spirogyra sp.2, and Spirogyra sp.3 from Nakhon Phanom province. The highest value of total phenolic compound was measured at 18.53±0.23 mg GAE/mg in Spirogyra sp. 2. The evaluation of antimicrobial activity of algal extracts against fungal Candida sp. and bacteria Staphylococcus aureus and Escherichia coli was performed by using the disk diffusion method along with determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC) and minimum bacterial concentration (MBC). The result of disk diffusion and MIC determination showed the efficiency of all extract samples against all tested strains at a concentration of 10 mg/mL. The most effective algal extract against Candida sp. showed with the MFC’s ranged from 10 to 20 mg/mL, whereas MBC of all extracts destroyed the two tested bacterial strains ranged from 10 to 20 mg/mL within 24 hours and up to 30 mg/mL after 48 hours. The results of this study support that Spirogyra spp. contains bioactive compounds that are the basis for further application in cosmeceuticals.

Comparison of Antifungal Activity of Thymus Vulgaris Essential Oil and Triple Antibiotic Paste Against Candida Albicans Isolated from Root Canal (In Vitro Study)

Background The main objective of chemomechanical endodontic therapy is to reduce or eliminate microorganisms from the root canal system, and intracanal medications are used to accelerate the disinfection process. The aim of this study this study was to assess the antifungal activity of thymus vulgaris essential oil against C. albicans compared to that of triple antibiotic paste. Materials and methods C. albicans was isolated from patients who required endodontic treatment. Using the agar well diffusion method, the efficacy of Thymus vulgaris essential oil against C. albicans was determined at 25 mg/ml, 10 mg/ml, 8 mg/ml, 6 mg/ml, 4 mg/ml, and 2 mg/ml and compared to the triple antibiotic paste. The minimum inhibitory and fungicidal concentrations against Candida albicans were determined using the microbroth dilution method. The constituents were identified using a gas chromatography–mass spectrometer. Results Thymus vulgaris essential oil demonstrated antifungal activity against C. albicans, which appeared to increase as the extract concentration increased, and the difference between all concentrations and triple antibiotic paste was significant (p ≤ 0.01). The MIC and MFC for Thymus vulgaris essential oil were 0.015 mg/ml and 0.031 mg/ml, respectively. 53 compounds were identified by (GC-MS) analysis, which represented more than 95% of the oil composition. The main component was thymol (35.48%). Conclusion Thymus vulgaris essential oil is effective against C. albicans, suggesting that it has the potential to be applied as an intracanal medication.

Analysis of the effectiveness of a new antimicrobial agent for disinfection in veterinary practice

The loss of effectiveness of standard treatment methods and the increased risk of rapid spread of infections are serious consequences of this problem. This underscores the need to develop new approaches to combating pathogen resistance and ensuring effective control of infections. Studies of antimicrobial activity were conducted on strains of C. albicans, A. niger, and B. subtilis. The minimal fungicidal concentration was determined based on the growth of microorganisms C. albicans, A. niger on Sabouraud agar media containing different concentrations of a new substance – a derivative of thiadiazole. The sporicidal activity was determined by culturing the test culture B. subtilis in meat-peptone broth, followed by seeding on meat-peptone agar. Sporicidal activity was determined by inoculating the test culture of B. subtilis into meat-peptone broth, followed by plating on meat-peptone agar. Control assays were performed by inoculating the test cultures on corresponding media without the test substances. The new disinfectant – a derivative of thiadiazole – demonstrated high antimicrobial activity. The aim of this research was to study the new chemical substance for antimicrobial (antifungal and sporicidal) activity and the creation of new types of biocides. The studies showed that the minimum fungicidal concentration of the 0.3% solution in a 30% alcohol solution against C. albicans RCPGY401 was 1.56 ± 1.06 μg/mL, A. niger 137a – 1.56 ± 1.29 μg/mL. Furthermore, the material exhibited sporicidal activity against B. subtilis ATCC 10702, with an effective concentration of – 3.12 ± 1.34 μg/mL. The research confirms the activity of the new compound against the studied microorganisms and allows for its recommendation for further study (treatment regimens, safety, control methods, etc.) for use in veterinary practice for various treatment purposes.

Profiling Key Aroma Compounds of Senecio glaucus L. and their Antimicrobial and Antioxidant Activities: Multiplex of GC-MS, NMR and In Silico Studies.

The essential oils of Senecio plants have been used to treat a wide range of ailments. The current study aimed to extract the essential oil of Senecio glaucus obtained from Egypt's Nile delta and determine its chemical profile using GC-MS and NMR analysis. Then, the antimicrobial activity of the oil has been investigated against different fungal and bacterial strains. In addition, its activity as radical scavenger has been evaluated using DPPH, ABTS, and metal chelating techniques. The results revealed the identification of 50 compounds representing 98.80 % of the oil total mass. Sesquiterpenes, including dehydrofukinone (27.15 %) and 4,5-di-epi-aristolochene (10.27 %), as well as monoterpenes, including p-cymene (4.77 %), represented the most predominant constituents. The dehydrofukinone has been isolated and structurally confirmed using 1D and 2D NMR techniques. The oil has showed remarkable antifungal activity against Candida glabrata and C. albicans where the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values were 3.13 μg/mL and 1.50 μg/mL and 12.50 μg/mL and 6.30 μg/mL, respectively that could be attributed to the sesquiterpene ketones present in the aerial tissues of the plant. Also, this oil inhibited the growth of the tested bacteria with MIC ranging from 12.50-100.00 μg/mL. In comparison to ascorbic acid and Trolox, the EO had remarkable scavenging activity of DPPH, ABTS and metal chelating with IC50 values of 313.17±13.4, 493.83±20.1, and 409.13±16.7 μg/mL. The docking studies of the identified compounds of the oil to different microbial targets, including Gyrase B and α-sterol demethylase, showed that the phytol possessed the best binding affinities toward the active sites of both enzymes with ΔG=-7.42 and -7.78 kcal/mol, respectively. In addition, the phytol revealed the highest binding affinity to tyrosine kinase Hck with ΔG=-7.44 kcal/mol.

The inhibitory effects of carvacrol, nystatin, and their combination on oral candidiasis isolates

BackgroundCandida, a common oral microbiota, can cause opportunistic fungal infections. With rising Candida infections and limited effective antifungals, new treatments are needed. This study investigates carvacrol essential oil’s effect on oral candidiasis, alone and with nystatin, compared to nystatin alone.Materials and methodsIn this study, oral samples were collected from dental clinic patients, especially denture users. The presence of Candida was confirmed and cultured from these samples. Candidiasis was detected by observing Candida colonies. Drug sensitivity was tested on 100 positive samples. The minimum concentration of inhibition and lethality of each isolate was evaluated using nystatin and carvacrol. The results were compared using two-way analysis of variance. Finally, the minimum inhibitory concentration (MIC) of nystatin and carvacrol was calculated individually and in combination.ResultsThe present study found that Candida albicans and non-albicans species were equally prevalent. Carvacrol showed significant biological activity against all Candida species, with an average MTT of 50.01%. The average MIC value of carvacrol was 24.96 µg/ml, indicating its potential to inhibit Candida growth. The mean Minimum Fungicidal Concentration (MFC) value of carvacrol was 23.48 µg/ml, suggesting its effectiveness in killing the fungi.ConclusionThe study’s findings reveal that the MIC of carvacrol was significantly lower than that of nystatin and the combination of nystatin and carvacrol. This suggests that carvacrol holds potential as an effective herbal remedy for candidiasis.

Anticandidal Activity of a Siderophore from Marine Endophyte Pseudomonas aeruginosa Mgrv7.

An endophytic symbiont P. aeruginosa-producing anticandidal siderophore was recovered from mangrove leaves for the first time. Production was optimal in a succinate medium supplemented with 0.4% citric acid and 15 µM iron at pH 7 and 35 °C after 60 h of fermentation. UV spectra of the acidic preparation after purification with Amberlite XAD-4 resin gave a peak at 400 nm, while the neutralized form gave a peak at 360 nm. A prominent peak with RP-HPLC was obtained at RT 18.95 min, confirming its homogeneity. It was pH stable at 5.0-9.5 and thermally stable at elevated temperatures, which encourages the possibility of its application in extreme environments. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) against Candida spp. Were in the range of 128 µg/mL and lower. It enhanced the intracellular iron accumulation with 3.2-4.2-fold (as judged by atomic absorption spectrometry) with a subsequent increase in the intracellular antioxidative enzymes SOD and CAT. Furthermore, the malondialdehyde (MDA) concentration due to cellular lipid peroxidation increased to 3.8-fold and 7.3-fold in C. albicans and C. tropicalis, respectively. The scanning electron microscope (SEM) confirmed cellular damage in the form of roughness, malformation, and production of defensive exopolysaccharides and/or proteins after exposure to siderophore. In conclusion, this anticandidal siderophore may be a promising biocontrol, nonpolluting agent against waterborne pathogens and pathogens of the skin. It indirectly kills Candida spp. by ferroptosis and mediation of hyperaccumulation of iron rather than directly attacking the cell targets, which triggers the activation of antioxidative enzymes.

Estimation of MBC: MIC Ratio of Herbal Extracts against Common Endodontic Pathogens

ABSTRACT Herbal extracts have evoked interest owing to the small number of terpenoids and phenolic compounds, which impart antimicrobial, antioxidant, and anti-inflammatory properties. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) of four herbal extracts (lemon grass oil, basil oil, peppermint oil, and Obicure tea extract) against endodontic pathogens along with the MIC: MBC/MFC ratio were evaluated. The antimicrobial activity by detecting the MIC of three essential oils and tea extract was evaluated against eight common endodontic pathogens by the broth dilution method, while MBC was detected by subculturing onto blood agar from the first –three to five tubes from the MIC dilution tubes (showing no turbidity), which were plated on blood agar. All herbal extracts proved to be effective antimicrobials against tested endodontic pathogens. Basil oil had a bacteriostatic effect on all the organisms (P &lt; 0.05). Mint oil showed bacteriostatic activity on Enterococcus (E.) faecalis and Peptostreptococcus (P &gt; 0.05). Tea extract had a bacteriostatic effect (P &gt; 0.05) against all tested microbes except Actinomyces, Lactobacilli, Staphylococcus (S.) aureus, and Fusobacterium (F.) nucleatum. Lemon grass oil had a bactericidal effect against all the organisms and a bacteriostatic effect against Peptostreptococcus (P &gt; 0.05). It can be concluded that basil oil showed a strong bactericidal effect on the test organisms. The MIC for the organisms ranged from 0.2 to 50 μg/ml.

In vitro inhibitory activity of Riparins against Candida spp. strains and in silico interaction with multi-drug-resistance proteins

Candida spp. includes opportunistic pathogens that are responsible for superficial and invasive infections. These strains have mechanisms of resistance against antimicrobials. Riparin compounds isolated from the green fruit of the plant Aniba riparia (Nees) Mez, are alkaloids with alkamide function with notable antimicrobial properties. We evaluated the inhibitory effect (in vitro) of Riparins isolated and combined with Fluconazole against strains of Candida albicans, C. tropicalis, and C. krusei; and in an in silico test, the anti-Candida activity of the factors MdR1, CdR1, and CdR2. Riparins were identified by 1D NMR spectroscopy (1H and 13C), electrospray ionization mass spectrometry (ESI-MS), and compared with previously reported spectral data. For the antifungal activity profile, the broth microdilution technique was used (1 - 1024µg/mL). For combined antifungal activity, Riparins were tested at fixed subinhibitory concentrations (RI, RII, and RIV of 256µg/mL and RIII, 64µg/mL), and FCZ, ranging from 1 - 1024µg/mL. Minimum Fungicide Concentration was performed by microculture in Petri dishes. For molecular docking, protein sequences were obtained from GenBank; targets were analyzed for homology, and model reliability was assessed using the Ramachandran plot. Composite stratification was performed by the MolDock Score, Rerank Score, PLANTS Score, and Vina Score. The results demonstrated that Riparins I, II, III, and IV, isolated or combined with FCZ have an inhibitory effect on Candida spp. cells, and a high probability of inhibiting antifungal resistance mechanisms, MdR1, CdR1, and CdR2.

Inorganic and organic chemical constituents of trona, alum and palm ash: Potential alternatives to conventional antifungal drugs?

There is high demand for the development of novel, effective, clinically safe and affordable antifungal agents to manage the ever emerging and re-emerging fungal infections. Natural compounds may be a source of novel chemical structures for development of antimicrobials. The aim of this study was to determine the inorganic and organic chemical constituents of trona, alum and palm ash; as potential alternatives to conventional antifungal drugs. The fungal isolates were obtained from high vaginal swab samples of patients suffering from vulvo-vaginal candidiasis. The isolates were identified based on their macroscopic, physiological, biochemical and molecular characteristics. The minimal inhibitory concentration (MIC) and minimal fungicidal concentrations (MFC) of the test agents were determined using the broth dilution method. Gas chromatography-mass spectroscopy (GC-MS) was used to determine the organic constituents; while x-ray fluorescence spectroscopy, for inorganic constituents. The isolates include Candida albicans, C. tropicalis, C. glabrata and C. parapsilosis. The MIC and MFC of alum against the isolates ranged from 12.50 mg/ml to 50 mg/ml, trona (6.25 mg/ml to 100 mg/ml) and palm ash (100 mg/ml to 200 mg/ml). Alum comprises oxides of sulphur (44.5 %), aluminium (14.49 %) while lead, arsenic and nickel all accounted for &lt;0.0010 %. The naturally occurring fatty acids include vaccenic acid (40.39 %), decanoic acid (13.21 %) and linoelaidic acid (9.84 %). Trona comprises of sulphur (2.14 %), chlorine (5.8 %), potassium (1.7 %), lead (0 %), arsenic and nickel (&lt;0.003 %); while the organic constituents include linoelaidic acid (32.99 %), nonanoic acid (14.81 %) and decanoic acid (6.8 %). The inorganic components of palm ash include potassium (28.8 %), sulphur (3.4 %), calcium (2.8 %) and chlorine (15 %) while the heavy metals all accounted for &lt;0.0007 %. The organic constituents were urea (8.65 %) and fatty acids (&lt;6 %). The antimicrobial properties of the natural compounds were probably due to their various organic and inorganic constituents; thus, could serve as potential raw materials in antifungal drugs production.

Antifungal activity against Candida albicans biofilm of Coffea robusta monofloral honey from Vietnam

Coffee (Coffea robusta) flower honey is one of the highest-yielding kinds of honey in Vietnam. Nevertheless, there is little research on the antifungal activity associated with this type of honey. Therefore, this study was conducted to investigate the antifungal activity against C. albicans of Vietnamese coffee monofloral honey and its potential effects on biofilm formation. This study was conducted using the broth microdilution method. The results showed that coffee flower honey was resistant to Candida albicans strain with minimum inhibitory concentration (MIC) and with minimum fungicidal concentration (MFC) values of 50% and 70% (w/v), respectively. No change in the antifungal activity of honey and the antifungal agent (Amphotericin B) against the C. albicans strain occurred after five consecutive exposures. When using SEM, honey at MIC (w/v) strongly affected the two stages of C. albicans biofilm formation. The surface structure of the biofilm, deformed, distorted, and atrophied phenotypes impacted by honey were also observed. Expression of transcriptional-level genes involved in biofilm formation, quorum-sensing, and stress survival was analyzed by RT-qPCR in honey-treated and untreated biofilms. The present study showed the antifungal activity of Vietnamese coffee flower honey against C. albicans.

Anti-fungal effects of novel N-(tert-butyl)-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine derivative and it's in-vitro, in-silico, and mode of action against Candida spp.

Imidazoles are a category of azole antifungals that encompass compounds such as ketoconazole, miconazole, esomeprazole, and clotrimazole. In contrast, the triazoles group, which includes fluconazole, voriconazole, and itraconazole, also plays a significant role. The rise of antibiotic resistance in fungal pathogens has evolved into a substantial global public health concern. In this study, two newly synthesized imidazo[1,2-a]pyridine derivative (Probe I and Probe II) molecules were investigated for its antimicrobial potency against of a panel of bacterial (Gram-positive and Gram-negative bacteria) and fungal pathogens. Among the different types of pathogens, we found that Probe II showed excellent antifungal activity against fungal pathogens, based on the preliminary screening the potent molecule further investigated against multidrug-resistance Candida sp. (n = 10) and compared with commercial molecules. In addition, in-silico molecular docking, its dynamics, absorption, distribution, metabolism, excretion and toxicity (ADMET) were analyzed. In this study, the small molecule (Probe II) displayed potent activity only against the Candida spp. including several multidrug-resistant Candida spp. Probe II exhibited minimum inhibitory concentration ranges from 4 to 16µg/mL and minimum fungicidal concentration in the range 4‒32µg/mL as the lowest concentration enough to eliminate the Candida spp. The selected molecules inhibit the formation of yeast to mold as well as ergosterol formation by the computational simulation against Sterol 14-alpha demethylase (CYP51) and inhibition of ergosterol biosynthesis by in-vitro model show that the Probe II completely inhibits the formation of ergosterol in yeast cells at 2× MIC. The ADMET analysis Probe II could be moderately toxic to the human being, though the in-vitro toxicity studies will help to understand the real-time toxic level. The novel compound Probe II, which was synthesized during the study, shows promise for development into a new generation of drug treatments aimed at addressing the emerging drug resistance in Candida sp.

Unravelling the Antimicrobial, Antibiofilm, Suppressing Fibronectin Binding Protein A (fnba) and cna Virulence Genes, Anti-Inflammatory and Antioxidant Potential of Biosynthesized Solanum lycopersicum Silver Nanoparticles.

Background and Objectives: Urinary tract infections [UTIs] are considered the third most known risk of infection in human health around the world. There is increasing appreciation for the pathogenicity of Gram-positive and Gram-negative strains in UTIs, aside from fungal infection, as they have numerous virulence factors. Materials and Methods: In this study, fifty urine samples were collected from patients suffering from UTI. Among the isolates of UTI microbes, six isolates were described as MDR isolates after an antibiotic susceptibility test carried out using ten different antibiotics. An alternative treatment for microbial elimination involved the use of biosynthesized silver nanoparticles (AgNPs) derived from Solanum lycopersicum [S. cumin]. Results: The sizes and shapes of AgNPs were characterized through TEM imaging, which showed spherical particles in a size range of 35-80 nm, of which the average size was 53 nm. Additionally, the silver nanoparticles (AgNPs) demonstrated inhibitory activity against Staphylococcus aureus (OR648079), exhibiting a 31 mm zone of inhibition at a minimum inhibitory concentration (MIC) of 4 mg/mL and a minimum bactericidal concentration (MBC) of 8 mg/mL. This was followed by Aspergillus niger (OR648075), which showed a 30 mm inhibition zone at an MIC of 16 mg/mL and a minimum fungicidal concentration (MFC) of 32 mg/mL. Then, Enterococcus faecalis (OR648078), Klebsiella pneumoniae (OR648081), and Acinetobacter baumannii (OR648080) each displayed a 29 mm zone of inhibition at an MIC of 8 mg/mL and an MBC of 16 mg/mL. The least inhibition was observed against Candida auris (OR648076), with a 25 mm inhibition zone at an MIC of 16 mg/mL and an MFC of 32 mg/mL. Furthermore, AgNPs at different concentrations removed DPPH and H2O2 at an IC50 value of 13.54 μg/mL. Also, AgNPs at 3 mg/mL showed remarkable DNA fragmentation in all bacterial strains except Enterococcus faecalis. The phytochemical analysis showed the presence of different active organic components in the plant extract, which concluded that rutin was 88.3 mg/g, garlic acid was 70.4 mg/g, and tannic acid was 23.7 mg/g. Finally, AgNPs concentrations in the range of 3-6 mg/mL showed decreased expression of two of the fundamental genes necessary for biofilm formation within Staphylococcus aureus, fnbA (6 folds), and Cna (12.5 folds) when compared with the RecA gene, which decreased by one-fold when compared with the control sample. These two genes were submitted with NCBI accession numbers [OR682119] and [OR682118], respectively. Conclusions: The findings from this study indicate that biosynthesized AgNPs from Solanum lycopersicum exhibit promising antimicrobial and antioxidant properties against UTI pathogens, including strains resistant to multiple antibiotics. This suggests their potential as an effective alternative treatment for UTIs. Further research is warranted to fully understand the mechanisms of action and to explore the therapeutic applications of these nanoparticles in combating UTIs.

In vitro antifungal activity of white thyme, oregano, and savory oils against five Monilinia fructicola isolates from the southeastern U.S.

Monilinia fructicola is a primary pathogen causing fruit brown rot of peach during pre- and post-harvest in the southeast of the United States. In this in vitro study, we assessed the antifungal activity of four plant essential oil (EO) treatments against five isolates of M. fructicola obtained from naturally infected peaches in Florida, Georgia, and South Carolina. The tested EOs were white thyme oil, oregano oil, summer savory oil, and a 1:1 mixture of thyme and oregano oils. We evaluated isolates’ growth using a Gompertz growth curve model. All tested EOs exhibited antifungal activity against all isolates, with thyme, oregano and the 1:1 mixture of thyme and oregano oils showing no significant differences and no evidence of synergy. Savory oil showed the least effectiveness and stability of the four EO treatments. We observed diverse sensitivities of different M. fructicola isolates to the EOs. The minimum inhibitory concentration values for the EOs ranged from 200 to 500 μL/L, while the minimum fungicidal concentration values varied from 500 to 750 μL/L, depending on the fungal isolate and EO treatment. All isolates were inhibited by the EOs at 500 μL/L and killed at 750 μL/L. Our findings provide a basis for future in vivo research on the use of these EOs for controlling fruit brown rot caused by M. fructicola in peach postharvest handling.

In vitro activity of the anthelmintic drug niclosamide against Sporothrix spp. strains with distinct genetic and antifungal susceptibility backgrounds.

The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings.

Unlocking the therapeutic potential of Carapa guianensis Aubl. (Meliaceae) leaves against Candida Sp.

Carapa guianensis Aubl., Meliaceae, is popularly known as andiroba, a plant species with wide therapeutic use, especially its fixed oil and leaves as a healing and anti-inflammatory agent. The work aimed to determine the antifungal and antioxidant activity of the extract and fractions of C. guianensis leaves. The leaves of C. guianensis collected in the municipality of São Luís, Maranhão, Brazil, were dried and pulverized. The powder was percolated with 70% ethanol, using a hydromodule of 1:12. The extract was developed with hexane and then partitioned (v/v) obtaining the following fractions: chloroform, ethyl acetate, and hydroethanol. The toxicological bioassay was carried out with Artemia salina and antifungal activity evaluated the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) with different species of the genus Candida. Toxicological tests showed progressive toxicity as partitioning was carried out. In the antifungal assay, the growth and death of C. albicans, C. glabrata, C. parapsilosis, and C. tropicalis were observed, demonstrating potential for use as an antifungal agent in pharmaceutical products.