Antifungal Studies Research Articles

Conventional Versus Microwave Induced Synthesis and Biological Evolution of Coumarin Substituted Thioaryl Pyrazolyl Pyrazoline

Aim: This is a comparative study of some new coumarin substituted thioaryl pyrazolyl pyrazoline. Methods: The target compounds were synthesized using both conventional as well as microwave irradiation by reaction of coumarin chalcones with different substituted hydrazine hydrates and aryl hydrazines to give the resultant pyrazoline derivatives. Microwave reaction, enhanced or-ganic reactions, and reduced reaction time led to better yields and selectivity than conventional methods. Results: The obtained compounds were characterized by different spectroscopic analysis includ-ing IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental-analysis and evaluated for their antimicrobial screening against a representative panel of bacteria (Bacillus subtilis, Staphylococ-cus aureus, Escherichia coli, Salmonella typhi) and fungi (Aspergillus niger, Candida albicans). Conclusion: In the present study, we have synthesized coumarin pyrazoline derivatives clubbed with benzofuran pyrazole via both conventional and microwave irradiation and also subjected to antibacterial and antifungal studies. Synthesis of target compounds by the microwave irradiation enhanced reaction rate and reduced reaction time led to better yields and selectivity than conven-tional methods. The study of antibacterial and antifungal activities revealed that all the com-pounds exhibited reasonable to excellent activities against the pathogenic strains.

Antifungal Activity of ZnO Nanobullets against Schizosaccharomyces pombe

In this study, an enhanced antifungal response of ZnO nanobullets (NBs) against Schizosaccharomyces pombe is reported. The ZnO NBs were prepared by alkali precipitation method and confirmed by microscopic, morphological and optical studies using SEM, EDX, TEM, HRTEM and photoluminescence (PL) spectroscopic techniques. Growth kinetics and MIC studies were conducted following the growth inhibition percentage studies. Colony forming assay, well diffusion, disc diffusion, N-acetyl cysteine (NAC) effect on S. pombe growth, trypan blue study, cellular reactive oxygen species (ROS) quantification using H2DCFDA dye, Bradford assay, DNA fragmentation and all other relevant protocols were performed in antifungal studies. ZnO nanobullets (NBs) were shown by SEM and TEM examinations to have an average size of 50 nm. The hexagonal wurtzite structure of ZnO NBs was confirmed by HRTEM’s lattice fringe findings. Defectrelated visible emissions at 412, 436, 457 and 564 nm were confirmed via PL analysis. It was found that ZnO NBs resulted in complete growth inhibition of S. pombe at 200 μg/mL. When S. pombe was treated with ZnO NBs, the Bradford assay revealed enhanced protein leakage, but the TBARS assay revealed lipid peroxidation brought on by reactive oxygen species (ROS). When S. pombe was exposed to ZnO NBs, the H2DCFDA assay revealed increased ROS generation, whilst the trypan blue assay revealed increased cell membrane fusion and lower viability. According to present study, the treatment with ZnO NBs caused S. pombe to develop damaged cell walls, leaky proteins and DNA breakage.

Luliconazole Loaded Niosomal Topical Gel: Factorial Design, in vitro Characterization and Antifungal Study

Luliconazole Loaded Niosomal Topical Gel: Factorial Design, in vitro Characterization and Antifungal Study

Synthesis, Characterization, Aggregation Behavior, Antifungal and Antibacterial Studies of a Novel Tetra-Metronidazole Substituted Zinc (II) Phthalocyanine

Synthesis, Characterization, Aggregation Behavior, Antifungal and Antibacterial Studies of a Novel Tetra-Metronidazole Substituted Zinc (II) Phthalocyanine

Design, synthesis and in vitro biological studies of novel triazoles with potent and broad-spectrum antifungal activity

A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. In vitro antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against Candida albicans SC5314, Cryptococcus neoformans 22-21, Candida glabrata 537 and Candida parapsilosis 22-20 with MIC values in the range of ≤0.125 µg/mL–4.0 µg/mL. In addition, compounds A1, A2, A6, A12 and A15 showed inhibitory activities against fluconazole-resistant Candida albicans and Candida auris. Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that A1, A3, and A9 interfered with the C. albicans ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of A3 and A9 with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.

Optical and biological activities of organic 4-chloroaniline derivative crystals

The organic aromatic acid 4-Chloroanilinium Bromide (CAB) and 4-Chloroanilinium Thiocyanate (CAT) crystals were grown using solution method in ethanol solvent at room temperature. The crystalline structural parameters of the grown CAB and CAT crystals were determined using single XRD study. The Gaussian 09 programme was applied to determine the molecular geometrical structure and second-order hyperpolarisability value. The linear optical property of the grown crystals was confirmed with the determined energy band gap value from Gaussian 09 programme as well as experimental UV-visible spectrum analysis. The calculated value of second-order hyperpolarisability from Gaussian 09 programme for nonlinear optical property is proved that the grown crystals are suitable candidates for optoelectronic device applications. The biological activity of the grown crystals was proved with antibacterial and antifungal studies and are promising candidates for the development of antibiotic drugs against tested bacterial strains and hence it is suitable for pharmaceutical applications.

High-efficiency fungal pathogen intervention for seed protection: new utility of long-chain alkyl gallates as heat-sensitizing agents.

Control of food-contaminating fungi, especially pathogens that produce mycotoxins, is problematic since effective method for intervening fungal infection on food crops is often limited. Generally Regarded As Safe (GRAS) chemicals, such as natural compounds or their structural derivatives, can be developed as antimicrobial agents for sustainable food/crop production. This study identified that long-chain alkyl gallates, i.e., octyl-, nonyl-, and decyl gallates (OG (octyl 3,4,5-trihydroxybenzoic acid), NG, DG), can function as heat-sensitizing agents that effectively prevent fungal contamination. Out of twenty-eight candidate compounds and six conventional antifungal agents examined, the heat-sensitizing capacity was unique to the long-chain alkyl gallates, where OG exhibited the highest activity, followed by DG and NG. Since OG is a GRAS compound classified by the United States Food and Drug Administration (FDA), further in vitro antifungal studies were performed using OG. When OG and mild heat (57.5°C) were co-administered for 90 seconds, the treatment achieved > 99.999% fungal death (> 5 log reduction). Application of either treatment alone was significantly less effective at reducing fungal survival. Of note, co-application of OG (3 mM) and mild heat (50°C) for 20 minutes completely prevented the survival of aflatoxigenic Aspergillus flavus contaminating crop seeds (Brassica rapa Pekinensis), while seed germination rate was unaffected. Heat-sensitization was also determined in selected bacterial strains (Escherichia coli, Agrobacterium tumefaciens). Altogether, OG is an effective heat-sensitizing agent for control of microbial pathogens. OG-mediated heat sensitization will improve the efficacy of antimicrobial practices, achieving safe, rapid, and cost-effective pathogen control in agriculture/food industry settings.

Design and Development of Sertaconazole Nitrate Loaded Silver Nanoparticulate Mucoadhesive Tablets for the Treatment of Vaginal Candidiasis

Vaginal candidiasis, a fungal infection estimates that 75 % of women will be suffering at least once during their lifetime. The disorders of this infection might be premature birth, pelvic inflammation, abortion, the transmission of sexual disorders, etc. In the present research, mucoadhesive vaginal tablets containing sertaconazole nitrate-loaded silver nanoparticles formulations were developed which increases the proximity period of the medicine with the vaginal mucosa, showing sustained drug release. The drug-loaded silver nanoparticle was synthesized by the chemical reduction method. There was successful conjugation of sertaconazole nitrate with silver nanoparticles (Ser-AgNP1) therefore, the drug’s solubility is increased by 2.51 folds. The confirmation of silver nanoparticles was accessed by UV-visible spectroscopy. The mucoadhesive vaginal tablets were formulated and evaluated for swelling index, mucoadhesive force, residence time, In vitro dissolution and release kinetics, stability, and antifungal study. Optimized batch F8 was selected based on optimum mucoadhesive force (2.59±0.25N), % swelling index (86.50±0.11%), and sustained drug release (95.63±0.16%) up to 12 hr and showed greater antifungal activity. Overall study reveals that a prepared novel formulation, a mucoadhesive vaginal tablet containing sertaconazole nitrate loaded silver nanoparticles prevail over sertaconazole nitrate poor solubility and delivered drug during an extended period of time and also improved antifungal activity against Candida albicans.

Synthesis and biological evaluation of coumarin appended thiazole hybrid heterocycles: Antibacterial and antifungal study

In the present investigation, a series of 3-(1-(2-(thiazol-2-yl)hydrazineylidene)ethyl)-2H-chromen-2-one derivatives are synthesized in good to excellent yield using PEG-400 as a reaction medium. The synthesized compounds are characterized by using different spectroscopic methods like FT-IR, 1H NMR, 13CMR, and HRMS. In this study, the synthesis and biological evaluation of a series of coumarin-appended thiazole hybrids were explored to assess their antibacterial and antifungal properties. Antibacterial activity of the synthesized coumarin-thiazole hybrids was screened against E. coli, P. aeruginosa, S. aureus, and S. pyogenes strains, while antifungal activity was screened against C. albicans, A. niger, and A. clavatus strains. Some of the synthesized compounds showed good antibacterial activity against E. coli and P. aeruginosa strains compared to standard drugs. The ADME profile of these compounds showed favorable pharmacological properties.

Biocomposite Coatings Doped with Magnesium and Zinc Ions in Chitosan Matrix for Antimicrobial Applications.

Hydroxyapatite doped with magnesium and zinc in chitosan matrix biocomposites have great potential for applications in space technology, aerospace, as well as in the biomedical field, as a result of coatings with multifunctional properties that meet the increased requirements for wide applications. In this study, coatings on titanium substrates were developed using hydroxyapatite doped with magnesium and zinc ions in a chitosan matrix (MgZnHAp_Ch). Valuable information concerning the surface morphology and chemical composition of MgZnHAp_Ch composite layers were obtained from studies that performed scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), metallographic microscopy, and atomic force microscopy (AFM). The wettability of the novel coatings, based on magnesium and zinc-doped biocomposites in a chitosan matrix on a titanium substrate, was evaluated by performing water contact angle studies. Furthermore, the swelling properties, together with the coating's adherence to the titanium substrate, were also analyzed. The AFM results emphasized that the composite layers exhibited the surface topography of a uniform layer, and that there were no evident cracks and fissures present on the investigated surface. Moreover, antifungal studies concerning the MgZnHAp_Ch coatings were also carried out. The data obtained from quantitative antifungal assays highlight the strong inhibitory effects of MgZnHAp_Ch against C. albicans. Additionally, our results underline that after 72 h of exposure, the MgZnHAp_Ch coatings display fungicidal features. Thus, the obtained results suggest that the MgZnHAp_Ch coatings possess the requisite properties that make them suitable for use in the development of new coatings with enhanced antifungal features.

Antifungal Dosing in Critically Ill Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) is an established advanced life support system, providing temporary cardiac and/or respiratory support in critically ill patients. Fungal infections are associated with increased mortality in patients on ECMO. Antifungal drug dosing for critically ill patients is highly challenging because of altered pharmacokinetics (PK). PK changes during critical illness; in particular, the drug volume of distribution (Vd) and clearance can be exacerbated by ECMO. This article discusses the available literature to inform adequate dosing of antifungals in this patient population. The number of antifungal PK studies in critically ill patients on ECMO is growing; currently available literature consists of case reports and studies with small sample sizes providing inconsistent findings, with scant or no data for some antifungals. Current data are insufficient to provide definitive empirical drug dosing guidance and use of dosing strategies derived from critically patients not on ECMO is reasonable. However, due to high PK variability, therapeutic drug monitoring should be considered where available in critically ill patients receiving ECMO to prevent subtherapeutic or toxic antifungal exposures.

In Silico Molecular Docking and In Vitro Antibacterial and Antifungal Study of Newly Synthesized Triazole Containing Heterocyclic Framework via Copper-Catalyzed Click Reaction

In Silico Molecular Docking and In Vitro Antibacterial and Antifungal Study of Newly Synthesized Triazole Containing Heterocyclic Framework via Copper-Catalyzed Click Reaction

Physicochemical and Anti-fungal Studies of the Pharmaceutical Co-crystal/Salt of Fluconazole.

Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt's thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π-π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains (Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.

High throughput biochemical profiling, and functional potential analysis for valorization of grape peduncles

Vitis vinifera L., commonly known as grape is a major fruit crop in the world. Grapes seem to confer health benefits due to their chemical components, biological and antioxidant activities. The present study is conducted to evaluate the biochemical constituents, antioxidant, and antimicrobial potential of ethanolic grape peduncles (EGP) extract. The result of phytochemical analysis revealed the presence of various phytochemicals such as flavonoid, tannin, carbohydrates, alkaloids, cardiac glycoside, phenol, steroid, terpenoids, quinones and anthraquinones. Furthermore, total phenolic content (TPC) and total flavonoid contents (TFC) were 7.35 ± 0.25 mg GAE/g (Gallic Acid Equivalent per gram) and 29.67 ± 0.13 mg QE/g (Quercetin Equivalent per gram) respectively. DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging assay revealed IC50 = 159.3 μg/mL. The antibacterial and antifungal study disclosed that the extract was highly potent against Salmonella typhi with maximum zone of inhibition of 27.2 ± 1.60 mm and Epidermophyton floccosum with 74 ± 1.81% inhibition. The extract was analyzed for its cytotoxicity and antileishmanial activity and showed no activity against HeLa cell line and promastigotes of Leishmania major. Elements Fe, Mn, Ni, Pb and Cd were determined by atomic absorption spectroscopy and approximately 50 compounds were identified by Gas Chromatography-Mass Spectrometry (GC–MS). Current work suggest that grape peduncles can be a promising source of bioactive medicinal component.

Biological function of sulfapyridine derivatives and their manganese(II) complexes

Three derivatives of Schiff bases, 6-chloro-chromensulfapyridine (CCSP), indol-3-sulfapyridine (ISP), and 5-chlorothiophen-2-sulfapyridine (CTSP), were synthesized and characterized by analytical, spectroscopic (IR, UV-Vis., 1H and 13C NMR, Mass, EPR), and electrochemical techniques. Antioxidant capabilities were recorded for both ligands and their Mn(II) complexes using DPPH scavenger and ascorbic acid as a reference. Compared with free ligands, the Mn(II) complexes exhibit greater antioxidant activity. In-vitro antibacterial and antifungal studies were performed by well diffusion technique. Results obtained from IC 50 value suggest that (CTCSP)2Mn (IC 50 = 210.8 μg/mL) has potent antimicrobials. In addition, in silico drug-likeness, absorption, distribution, metabolism, and excretion (ADME) properties were examined for the ligands and complexes.

Antioxidant and antifungal efficacy of green synthesized silver nanoparticles

The use of herbs have gained momentum in the contemporary research, as they possess several biological activities. Green synthesised nanoparticles are extensively under exploration due to their multi-faceted roles. The present work details the comparative antioxidant potentials of the leaves and seeds extracts of the herbs Coriander sativum (coriander), Trachyspermum ammi (Ajwain), Trigonella foenum-graecum (menthi) and synthesis of silver nanoparticles. The antifungal effects of the synthesized nanoparticles against a pathogenic species of Aspergillus flavus and the mode of action was also analysed. Results of the investigation showed that the seed extract of Ajwain and leaf extract of coriander exhibited the highest antioxidant properties and were used as reducing agents for silver nanoparticles synthesis. The nanoparticles were characterized by UV-visible absorption spectrum, Scanning Electron Microscopy-Energy Dispersive Spectra (SEM-EDS) and Transmission Electron Microscopy (TEM). The silver nanoparticles showed enhanced antioxidant activity when compared to the extracts. The antifungal studies showed that both the nanoparticles were effective against A. flavus, while C. sativum silver nanoparticle (Cs-AgNP) exhibited the highest activity. The mechanism of antifungal effect showed that the nanoparticles exerted a membranolytic activity on the pathogenic A. flavus. SEM images showed highly wrinkled mycelia in nanoparticles-treated samples and membrane permeabilization was evident from the 1- N-phenyl napththyl amine assay in nanoparticle-treated fungal samples. The activity of a transmembrane enzyme calcium ATPase was also significantly decreased in treated samples confirming the membrane damage effects of nanoparticles. Among the nanoparticles, Cs-AgNP showed the maximum effect. The efficacy of these green synthesized nanoparticles provides insight into their use as effective antifungal agents.

Synthesis of Aminoalkyl Sclareolide Derivatives and Antifungal Activity Studies.

Sclareolide was developed as an efficient C-nucleophilic reagent for an asymmetric Mannich addition reaction with a series of N-tert-butylsulfinyl aldimines. The Mannich reaction was carried out under mild conditions, affording the corresponding aminoalkyl sclareolide derivatives with up to 98% yield and 98:2:0:0 diastereoselectivity. Furthermore, the reaction could be performed on a gram scale without any reduction in yield and diastereoselectivity. Additionally, deprotection of the obtained Mannich addition products to give the target sclareolide derivatives bearing a free N-H group was demonstrated. In addition, target compounds 4-6 were subjected to an antifungal assay in vitro, which showed considerable antifungal activity against forest pathogenic fungi.

Studies on Antifungal Properties of Methacrylamido Propyl Trimethyl Ammonium Chloride Polycations and Their Toxicity In Vitro.

The biological activity of polycations is usually associated with their biocidal properties. Their antibacterial features are well known, but in this work, observations on the antifungal properties of macromolecules obtained by methacrylamido propyl trimethyl ammonium chloride (MAPTAC) polymerization are presented. The results, not previously reported, make it possible to correlate antifungal properties directly with the structure of the macromolecule, in particular the molecular mass. The polymers described here have antifungal activity against some filamentous fungi. The strongest effect occurs for polymers with a mass of about 0.5 mDa which have confirmed activity against the multidrug-resistant species Scopulariopsis brevicaulis, Fusarium oxysporum, and Fusarium solani, as well as the dermatophytes Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton interdigitale, and Trichophyton tonsurans. In addition, this publication describes the effects of these macromolecular systems on serum and blood components and provides a preliminary assessment of toxicity on cell lines of skin-forming cells, i.e., fibroblasts and keratinocytes. Additionally, using a Franz diffusion chamber, a negligibly low transport of the active polymer through the skin was demonstrated, which is a desirable effect for externally applied antifungal drugs. IMPORTANCE Infectious diseases are a very big medical, social, and economic problem. Even before the COVID-19 pandemic, certain infections were among of the most common causes of death. The difficulties in the treatment of infectious diseases concern in particular fungal diseases, against which we have only a few classes of drugs represented by a few substances. The publication presents the preliminary results of the in vitro antifungal activity studies of four MAPTAC polymers on different fungal species and their cytotoxicity to human cells (fibroblasts and keratinocytes). The paper also compares these properties with analogous ones of two commonly used antifungal drugs, ciclopirox and terbinafine.

Identification of effective plant extracts against candidiasis: an in silico and in vitro approach

BackgroundGlobally, millions of people suffer from repeated fungal infections affecting the skin, keratinized tissues, and mucosal membranes. Approximately 1.7 million cases result in death with an elevated incidence rate among immunocompromised people that may later result in severe infections. Among the causative agents, Candida albicans are the most prevalent fungi inducing subcutaneous to invasive candidiasis. Although they are commensals in human body alteration in gut or prolonged treatments results in candidiasis. Several virulence proteins of C. albicans are involved in infections and secreted aspartic proteases2 (SAP2) plays an important role among them by causing damage to the reconstituted human epithelium. In the present study, phytochemicals from Heliotropium indicum, Grona triflora, Ziziphus mauritiana, Atalantia racemosa, Coccinia grandis, Caryota urens, Aristolochia bracteolata, Evolvulus alsinoides, Pyrus communis and Commelina benghalensis were studied against SAP2 with the help of bioinformatic tools to understand their binding efficiency.ResultsThe phytochemical structures were retrieved from PubChem database and the target protein structure was retrieved from PDB database with ID:3PVK. ADME profiling for phytochemicals was performed with Qikprop module, followed by docking with protein using Schrodinger software. Docking studies showed that Indicine-N-Oxide from H. indicum scored the significant glide score of − 5.54 kcal/mol. Finally, antifungal studies against C. albicans were conducted using several extracts of plants containing phytochemicals with considerable glide scores on docking studies. The Ethyl acetate leaf extract of H. indicum prominently inhibited the fungal growth when compared with the control.ConclusionIdentification of effective therapeutic candidates for the treatment of fungal infection is facilitated by the potential of H. indicum to hinder fungal growth and the interaction of their phytocompounds with fungal targets paves a way for developing a novel drug.

Design, Development, and Evaluation of Constant Voltage Iontophoresis for the Transungual Delivery of Efinaconazole.

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1-E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol®) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol®, and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage (p-0.0001) and enhancer concentration (p-0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant (p < 0.0001) enhancement in the permeation (~78.59 µg/cm2) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte. Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.