Antifungal Mode Of Action Research Articles

Inhibitory effects and mode of antifungal action of isobavachalcone on Candida albicans growth and virulence factors

The fungus Candida albicans causes various kinds of human infections, including oral thrush, vulvovaginitis and life-endangering bloodstream infections, the incidence of which are rising. Worsening this, the clinical antifungals are limited to a few, highlighting the necessity to develop novel antifungal therapies. In this study, the antifungal activities of isobavachalcone against C. albicans SC5314 and nine C. albicans clinical isolates were tested. The effects of isobavachalcone (IBC) on C. albicans virulence factors, such as hyphal formation, adhesion, biofilm formation and extracellular phospholipase production, as well as the underlying mechanism, were also evaluated. Antifungal susceptibility test revealed that IBC has significant anti-Candida activities, with both MIC and MFC being 4–5 μg/mL against all strains tested. Hyphal formation in RPMI-1640, Spider and GlcNAc medium, adhesion to abiotic polystyrene surfaces and surfaces of A549 cells, could be inhibited by IBC. Most important, IBC could inhibit the C. albicans biofilm formation and development. PI staining tests showed that IBC could increase the cell membrane permeability, suggesting the damages to the fungal cell membrane. IBC was further demonstrated to induce excessive ROS production in C. albicans planktonic cells and its mature biofilms, as revealed by DCFH fluorescence detection through flowcytometry and relative fluorescence intensity analysis (with a microplate reader). The roles of ROS in the antifungal activity of IBC were further confirmed through antioxidant rescue assays in MIC and biofilm formation tests. Compared to its antifungal activity, the cytotoxicity against mammalian cells was low, indicating its potential in developing antifungal therapies.

Antifungal Activity of Disalt of Epipyrone A from Epicoccum nigrum Likely via Disrupted Fatty Acid Elongation and Sphingolipid Biosynthesis.

Multidrug-resistant fungal pathogens and antifungal drug toxicity have challenged our current ability to fight fungal infections. Therefore, there is a strong global demand for novel antifungal molecules with the distinct mode of action and specificity to service the medical and agricultural sectors. Polyenes are a class of antifungal drugs with the broadest spectrum of activity among the current antifungal drugs. Epipyrone A, a water-soluble antifungal molecule with a unique, linear polyene structure, was isolated from the fungus Epiccocum nigrum. Since small changes in a compound structure can significantly alter its cell target and mode of action, we present here a study on the antifungal mode of action of the disalt of epipyrone A (DEA) using chemical-genetic profiling, fluorescence microscopy, and metabolomics. Our results suggest the disruption of sphingolipid/fatty acid biosynthesis to be the primary mode of action of DEA, followed by the intracellular accumulation of toxic phenolic compounds, in particular p-toluic acid (4-methylbenzoic acid). Although membrane ergosterol is known to be the main cell target for polyene antifungal drugs, we found little evidence to support that is the case for DEA. Sphingolipids, on the other hand, are known for their important roles in fungal cell physiology, and their biosynthesis has been recognized as a potential fungal-specific cell target for the development of new antifungal drugs.

Mechanistic insights into antifungal potential of Alexidine dihydrochloride and hexachlorophene in Candida albicans: a drug repurposing approach.

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66-24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans.

Fungal membrane determinants affecting sensitivity to antifungal cyclic lipopeptides from Bacillus spp.

Bacillus spp. produce numerous antimicrobial metabolites. Among these metabolites, cyclic lipopeptides (CLP) including fengycins, iturins, and surfactins are known to have varying antifungal activity against phytopathogenic fungi. The differential activities of CLP have been attributed to diverse mechanisms of action on fungal membranes. However, the precise biochemical determinants driving their antifungal modes of action have not been conclusively identified. In this study, three plant pathogenic fungi of varying lipopeptide sensitivities, Alternaria solani, Cladosporium cucumerinum, and Fusarium sambucinum, were studied to determine how their cell membrane lipid compositions may confer sensitivity and/or tolerance to fengycin, iturin, and surfactin. Results indicated that sensitivity to all three lipopeptides correlated with lower ergosterol content and elevated phospholipid fatty acid unsaturation. Fungal sensitivity to surfactin was also notably different than fengycin and iturin, as surfactin was influenced more by lower phosphatidylethanolamine amounts, higher levels of phosphatidylinositol, and less by phospholipid fatty acyl chain length. Results from this study provide insight into the fungal membrane composition of A. solani, F. sambucinum, and C. cucumerinum and the specific membrane characteristics influencing the antifungal effectiveness of fengycin, iturin, and surfactin. Understanding of these determinants should enable more accurate prediction of sensitivity-tolerance outcomes for other fungal species exposed to these important CLP.

Conazoles

Conazoles belong to the group of azole-based fungicides and pharmaceutical preparations that are widely used in agriculture for crop protection and in human and veterinary medicine for the treatment of oropharyngeal and urogenital mycotic infections. The antifungal mode of action consists in the inhibition of certain cytochrome c-oxidase enzymes leading to disruption of the ergosterol metabolic pathway, which plays a similar role in cholesterol synthesis in mammals. Some conazoles possess hepatotoxic properties, some are mutagenic and tumorigenic, some are only carcinogenic and some do not act in these negative ways. In addition, their potential for cumulative exposure and deposition of residues in the human body could contribute to an increased risk of certain diseases and adverse health conditions, particularly during the foetal development. For these reasons, the risk assessment of the use of conazoles in human medicine and plant protection requires harmonisation and further research.

A synthetic peptide mimic kills Candida albicans and synergistically prevents infection

More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited. Here we investigate the antifungal mode of action and therapeutic potential of positively charged, synthetic peptide mimics to combat Candida albicans infections. Our data indicates that these synthetic polymers cause endoplasmic reticulum stress and affect protein glycosylation, a mode of action distinct from currently approved antifungal drugs. The most promising polymer composition damaged the mannan layer of the cell wall, with additional membrane-disrupting activity. The synergistic combination of the polymer with caspofungin prevented infection of human epithelial cells in vitro, improved fungal clearance by human macrophages, and significantly increased host survival in a Galleria mellonella model of systemic candidiasis. Additionally, prolonged exposure of C. albicans to the synergistic combination of polymer and caspofungin did not lead to the evolution of tolerant strains in vitro. Together, this work highlights the enormous potential of these synthetic peptide mimics to be used as novel antifungal formulations as well as adjunctive antifungal therapy.

Unmasking the Antifungal Activity of Anacardium occidentale Leaf Extract against Candida albicans.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis.

Utilizing zinc oxide nanoparticles as an environmentally safe biosystem to mitigate mycotoxicity and suppress Fusarium graminearium colonization in wheat

The biosynthesis of zinc oxide nanoparticles (ZnONPs) offers great potential for plant disease management due to their potent antimicrobial properties and environmental safety. However, the precise mechanisms underlying their antifungal mode of action and role in suppressing mycotoxins remain unclear. This study aims to elucidate the mechanisms by which ZnONPs suppress the pathogenic fungus Fusarium graminearium, known to cause Fusarium head blight in wheat. Additionally, it investigates how ZnONPs mitigate the production of mycotoxins, which pose risks to humans and ruminants. The study demonstrates that ZnONPs, bioproduced by Pseudomonas poae (P. poae), inhibit not only fungal growth, colony formation, and spore germination, but also significantly reduce mycotoxin production of F. graminearium by inhibiting the synthesis of deoxynivalenol (DON), downregulating the FgTRI gene, and causing morphological alterations of the toxisomes. The results also highlight that ZnONPs exert significant effects on fungi through multiple mechanisms, including cell wall damage and the generation of reactive oxygen species (ROS). Moreover, ZnONPs effectively inhibit F. graminearium in wheat leaves and coleoptiles. Fluorescence microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and optical microscopy all show that ZnONPs stop F. graminearium from getting into wheat plants and colonising them. Overall, the findings of this study provide evidence that ZnONPs are highly effective in reducing F. graminearium colonization in wheat plants and effectively decreasing mycotoxin production through multiple pathways.

A novel pH-responsive monomer inhibits Candida albicans via a dual antifungal mode of action.

The scarcity of the antifungal drug arsenal highlights an urgent need to develop alternative treatments for candidiasis caused by Candida albicans (C. albicans). As pH is closely associated with C. albicans infection, it could be an essential target in a novel approach for designing antifungal therapy. In this study, a novel intelligent antifungal monomer, dodecylmethylaminoethyl methacrylate (DMAEM), with a pH-responsive tertiary amine group and a methacrylate-derived CC double bond group is developed. It is uncovered that the two functional groups of DMAEM contribute to a dual mode of action. Under acidic pH, the tertiary amine of DMAEM protonates into a cationic fungicide, sharing similar structural and functional characteristics with quaternary ammonium salts, which exerts fungicidal activity by targeting the CHK1 two-component system in C. albicans. At neutral pH, the methacrylate-derived CC double bond group contributes to anti-virulence activity by blocking hyphal formation. In addition, it is also identified that DMAEM suppresses filamentation by altering the extracellular vesicles of C. albicans. These findings support that the novel intelligent pH-responsive monomer could be a therapeutic candidate for treating candidiasis.

Bioinorganic chemistry of shepherin II complexes helps to fight Candida albicans?

The fungal cell wall and cell membrane are an important target for antifungal therapies, and a needle-like cell wall or membrane disruption may be an entirely novel antifungal mode of action. In this work, we show how the coordination of Zn(II) triggers the antifungal properties of shepherin II, a glycine- and histidine-rich antimicrobial peptide from the root of Capsella bursa-pastoris. We analyze Cu(II) and Zn(II) complexes of this peptide using experimental and theoretical methods, such as: mass spectrometry, potentiometry, UV–Vis and CD spectroscopies, AFM imaging, biological activity tests and DFT calculations in order to understand the correlation between their metal binding mode, structure, morphology and biological activity. We observe that Zn(II) coordinates to Shep II and causes a structural change, resulting in fibril formation, what has a pronounced biological consequence – a strong anticandidal activity. This phenomenon was observed neither for the peptide itself, nor for its copper(II) complex. The Zn(II) – shepherin II complex can be considered as a starting point for further anticandidal drug discovery, which is extremely important in the era of increasing antifungal drug resistance.

Cardamom oil-infused paper box: Enhancing rambutan fruit post-harvest disease control with reusable packaging

The research aimed to develop a paper box with 10–300 μl of cardamom oil to improve rambutan storage, reduce waste, and explore reuse possibilities. The experiment investigated the delay in mold growth caused by the post-harvest disease, Pestalotiopsis sp., both on the medium and on rambutan fruit under storage conditions of 10 ± 2 °C and approximately 80% RH. The results showed that CM at 300 μl significantly inhibited Pestalotiopsis sp. mycelium and spore germination on the medium, while a lower volume of 30 μl effectively delayed mold incidence on rambutan during the 14-day storage period. The confirmed antifungal mode of action indicated that CM disrupted Pestalotiopsis sp. ergosterol and cell membrane integrity, resulting in mycelium lysis and damaged morphology, thereby inhibiting its growth. The active fruit box can be reused for at least 2 or 3 storage cycles, effectively delaying rambutan decay and preserving its color change parameters. By using the box with 30 μl of CM, rambutan's shelf-life was extended to 14 days compared to the control's shelf-life of around 7 days. Active paper boxes offer a valuable solution for improving post-harvest fruit storage and transportation, benefiting both farmers and consumers.

Deciphering Staphylococcus xylosus and Staphylococcus equorum mode of action against Penicillium nordicum in a dry-cured ham model system

Penicillium nordicum is one of the major producers of ochratoxin A (OTA) in dry-cured ham. Staphylococcus xylosus Sx8 and Staphylococcus equorum Se31 have been previously proposed as biocontrol agents (BCAs) to prevent the OTA contamination, although their antifungal mode of action has not been established yet. Thus, the aim of this work was to elucidate their mode of action against P. nordicum in a dry-cured ham model system. For this, the effect of live cells, dead cells, and cell-free broth; the nutritional utilisation pattern, niche overlap index (NOI), interactions by dual-culture assays, antifungal effect of volatile compounds, OTA detoxification, and effect on fungal proteome were determined. No fungal growth was observed after 14 days of co-culture with live cells of each staphylococcus at 15 or 20 °C. However, such inhibition was not observed with either dead cells or extracellular extracts. The number of carbon sources utilised by P. nordicum was higher than those used by both cocci at 20 °C, whilst the opposite occurred at 15 °C. According to NOI, nutritional dominance depends on temperature, at 20 °C P. nordicum dominated the niche, but at 15 °C the mould is dominated by the BCAs. The volatile pattern generated by each coccus did not show antifungal effect, and both staphylococci failed to degrade or adsorb OTA. However, in the interaction assay, S. xylosus and S. equorum were able to decrease the fungal growth and its OTA production. In addition, proteomic analyses showed changes in the abundance of proteins related to the cell wall integrity (CWI), carbohydrate metabolism and the biosynthesis of secondary metabolites such as OTA. In conclusion, overall, the antagonistic effects of the two studied cocci against P. nordicum are greater at 15 °C than at 20 °C, being linked to competition for space and nutrients, triggering alterations in CWI pathway, OTA biosynthesis, and carbohydrate metabolism.

P-Aminobenzoic acid inhibits the growth of soybean pathogen Xanthomonas axonopodis pv. glycines by altering outer membrane integrity.

p-Aminobenzoic acid (pABA) is an environmentally friendly bioactive metabolite synthesized by Lysobacter antibioticus. This compound showed an unusual antifungal mode of action based on cytokinesis inhibition. However, the potential antibacterial properties of pABA remain unexplored. In this study, pABA showed antibacterial activity against Gram-negative bacteria. This metabolite inhibited growth (EC50 = 4.02 mM), and reduced swimming motility, extracellular protease activity, and biofilm formation in the soybean pathogen Xanthomonas axonopodis pv. glycines (Xag). Although pABA was previously reported to inhibit fungal cell division, no apparent effect was observed on Xag cell division genes. Instead, pABA reduced the expression of various membrane integrity-related genes, such as cirA, czcA, czcB, emrE, and tolC. Consistently, scanning electron microscopy observations revealed that pABA caused major alternations in Xag morphology and blocked the formation of bacterial consortiums. In addition, pABA reduced the content and profile of outer membrane proteins and lipopolysaccharides in Xag, which may explain the observed effects. Preventive and curative applications of 10 mM pABA reduced Xag symptoms in soybean plants by 52.1% and 75.2%, respectively. The antibacterial properties of pABA were studied for the first time, revealing new insights into its potential application for the management of bacterial pathogens. Although pABA was previously reported to show an antifungal mode of action based on cytokinesis inhibition, this compound inhibited Xag growth by altering the outer membrane's integrity. © 2023 Society of Chemical Industry.

The potential role of plant secondary metabolites on antifungal and immunomodulatory effect.

With the widespread use of antibiotic drugs worldwide and the global increase in the number of immunodeficient patients, fungal infections have become a serious threat to global public health security. Moreover, the evolution of fungal resistance to existing antifungal drugs is on the rise. To address these issues, the development of new antifungal drugs or fungal inhibitors needs to be targeted urgently. Plant secondary metabolites are characterized by a wide variety of chemical structures, low price, high availability, high antimicrobial activity, and few side effects. Therefore, plant secondary metabolites may be important resources for the identification and development of novel antifungal drugs. However, there are few studies to summarize those contents. In this review, the antifungal modes of action of plant secondary metabolites toward different types of fungi and fungal infections are covered, as well as highlighting immunomodulatory effects on the human body. This review of the literature should lay the foundation for research into new antifungal drugs and the discovery of new targets. KEY POINTS: • Immunocompromised patients who are infected the drug-resistant fungi are increasing. • Plant secondary metabolites toward various fungal targets are covered. • Plant secondary metabolites with immunomodulatory effect are verified in vivo.

Synthesis of Pogostone-Inspired Dehydroacetic Acid Derivatives and Their Antifungal Activity against Sclerotinia sclerotiorum (Lib.) de Bary.

In an effort to exploit the natural antifungal pogostone, its simplified scaffold dehydroacetic acid (DHA) was used as a lead compound to semi-synthesize 56 DHA derivatives (I1-48, II, III, and IV1-6). Among them, compound IV4 exhibited the most potent antifungal activity with 11.0 μM EC50 against mycelial growth of Sclerotinia sclerotiorum (Lib.) de Bary whose sclerotia production was also completely suppressed at this concentration. Furthermore, IV4 could completely inhibit infection cushion formation of S. sclerotiorum on rape leaves and achieved a preventive efficacy of 90.2 % at 500 μM, which was on the same level as that of commercial boscalid at 30 μM (88.7 %). The results of physiological and ultrastructural studies indicated that IV4 might disrupt the cell membrane permeability or induce the imbalance of mitochondrial membrane potential homeostasis to exert the antifungal mode of action. Besides, the robust and predicative three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed and discussed herein.

Antifungal mode of action of bay, allspice, and ajowan essential oils and their constituents against Colletotrichum gloeosporioides via overproduction of reactive oxygen species and downregulation of ergosterol biosynthetic genes

This study was conducted to investigate the antifungal activity of 135 plant essential oils (EOs) and their constituents against Colletotrichum gloeosporioides (Penz.) Penz. and Sacc. Among the EOs, bay (Pimenta racemosa), allspice (Pimenta dioica), and ajowan (Trachyspermum ammi) showed 100 % inhibition of C. gloeosporioides at 10, 5, and 5 μl/paper disc, respectively. Of their constituents, (-)-α-pinene, (+)-α-pinene, thymol, eugenol, isoeugenol, 4-allylphenol, and carvacrol exhibited 100 % inhibition of growth at 10, 10, 10, 5, 5, 2.5, and 1.25 μl/paper disc, respectively. In an antifungal bioassay of artificial blends, eugenol, 4-allylphenol, and thymol were determined to be the major contributors to the antifungal activity of bay, allspice, and ajowan EOs. Confocal laser scanning microscopy images indicate the overproduction of reactive oxygen species (ROS) and cell membrane disruption in C. gloeosporioides treated with the EOs or their constituents. In addition, a decrease in ergosterol content and downregulation of ergosterol biosynthetic genes were confirmed in treated C. gloeosporioides. Based on these results, we attribute the antifungal actions of bay, allspice, and ajowan EOs and their active constituents to ROS generation and downregulation of ergosterol biosynthetic genes.

Biosensor-Enabled Discovery of CaERG6 Inhibitors and Their Antifungal Mode of Action against Candida albicans.

Fungal infections caused by opportunistic pathogens, such as Candida albicans, are generally underappreciated by the public in spite of their high mortality rates. Antifungal arsenals are extremely limited. Herein, based on biosynthetic pathway comparison and functional characterization, CaERG6, a crucial sterol 24-C-methyltransferase involved in the biosynthesis of ubiquitous ergosterol in C. albicans, was set up as an antifungal target. CaERG6 inhibitors were identified from the in-house small-molecule library by a biosensor-based high-throughput screening. The CaERG6 inhibitor NP256 (palustrisoic acid E) is a potential antifungal natural product that acts by inhibiting ergosterol biosynthesis, downregulating the gene expression level in hyphal formation, blocking biofilm formation, and disrupting morphological transition in C. albicans. NP256 enhances C. albicans susceptibility to some known antifungals significantly. The present study demonstrated the CaERG6 inhibitor NP256 as a potential class of antifungal compound for monotherapy or combinatory therapy.

Antifungal activity of 40 plant essential oil components against Diaporthe fusicola from postharvest kiwifruits and their possible action mode

The antifungal activity of essential oils is closely related to their components and contents. The study aimed to explore the structural activity of essential oil (EO) components against Diaporthe fusicola and modes of action. The results showed most of the tested compounds showed inhibitory effects on the growth of D. fusicola and carvacrol was the strongest one with half maximal effective concentration (EC50) of 11.21 μL/L. The chemical structures of the tested compounds had great influences on their antifungal activity, in which the presence of CHO group, CC group or Ar-OH group in any EO components significantly increase the antifungal potency, but the increment of carbon chain length of saturated fatty aldehyde decreased antifungal activity. In order to analyze the antifungal action mode of EO components, the correlations between EC50 and oxidation-reduction potential (ORP), cell-membrane permeability and respiration inhibition of the tested compounds were further evaluated. The results showed antifungal activities of these EO components seemed to be accomplished by increase of cell membrane permeability and inhibition of the respiration of D. fusicola. The levels of increased membrane permeability, inhibited respiration and ORP of chemicals were all significantly correlated with EC50. This results indicated the action mode of these EO components against D. fusicola may be associated with the increment of cell membrane permeability and respiration inhibition via disrupting redox homeostasis in fungal cells, and oxidation-reduction property could be used as a secondary indicator for screening the antifungal agent from EO components.

Synthesis of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl) propan-2-ol as potential antifungal and antitubercular agents

The intense pressure of resistance to antibiotics leads the whole world's health security to drastic conditions due to Mycobacterial and fungal infections. To search for potent antifungal and antitubercular lead compounds, the synthesis of a new series of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol, (9a-l) derivatives by click reaction of 1-azido-2-(quinolin-4-yl)propan-2-ol, (7a-d) and substituted ethynylbenzene (8a-c) is reported. The structures of the novel synthesized 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol derivatives were characterized by 1H NMR, 13C NMR spectroscopic and Mass spectrometric analysis. The synthesized compounds were examined for antifungal activity against C. albicans (NCIM 3100), A. niger (ATCC 504) and antitubercular activity against Mycobacterium tuberculosis H37Rv (MTB) (ATCC 25177). Eleven derivatives showed good to excellent antifungal activity against A. niger with MIC 7.81–62.5 ​μg/mL. To study the plausible antifungal mode of action, compounds 9e, 9f, 9g, 9i, and 9k were further evaluated for the ergosterol biosynthesis inhibition activity. All these compounds showed ergosterol biosynthesis inhibition activity. All twelve derivatives of 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol, (9a-l) showcased excellent antitubercular activity against M. tuberculosis H37Rv with MIC 1.6–3.2 ​μg/mL. No significant cytotoxic activity was displayed by these novel derivatives against l929 mouse fibroblast cells. The potential antifungal and antitubercular activities compelled the conclusion that the 2-(6-substituted quinolin-4-yl)-1-(4-aryl-1H-1,2,3-triazol-1-yl)propan-2-ol derivatives could assist in the development of lead compounds for the treatment of tuberculosis and fungal infections.

Preparation and characterization of a novel nanoemulsion consisting of chitosan and Cinnamomum tamala essential oil and its effect on shelf-life lengthening of stored millets

This study aimed to improve the stability of Cinnamomum tamala essential oil (CTEO) via encapsulating into chitosan nanoemulsion (CsNe) through an ionic-gelation technique and explore its food preservative efficacy against aflatoxigenic strain of Aspergillus flavus (AFLHPSi-1, isolated from stored millet), aflatoxin B1 (AFB1) contamination, and lipid peroxidation, causing qualitative deterioration of stored millets. The CTEO was characterized through gas chromatography–mass spectrometry (GC–MS) analysis that confirmed the presence of linalool as a major component occupying approximately 82.64% of the total oil. The synthesized nanoparticles were characterized through scanning electron microscopy (SEM), fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) analysis. The encapsulation efficiency (EE) and loading capacity (LC) of CTEO-CsNe were found to be 97.71% and 3.33%, respectively. In vitro release study showed a biphasic release pattern: with an initial burst release followed by a controlled release of CTEO. During investigation of efficacy, the CTEO-CsNe caused complete inhibition of A. flavus growth, and AFB1 biosynthesis at 1.0 and 0.8 μL/mL, respectively. The CTEO-CsNe exhibited its antifungal mode of action by altering fungal plasma membrane integrity (ergosterol inhibition) and permeability (leakage of important cellular constituents), and antiaflatoxigenic mode of action by inhibiting cellular methylglyoxal biosynthesis. CTEO-CsNe showed high free radical scavenging capacity (IC50 = 5.08 and 2.56 μL/mL) against DPPH•+ and ABTS•+ radicals, respectively. In addition, CTEO-CsNe presented remarkable preservative efficacy, inhibiting AFB1 and lipid peroxidation in model food system (Setaria italica) without altering their organoleptic properties. Based on overall results, CTEO-CsNe can be recommended as a novel shelf-life enhancer of stored millet samples.