Antifungal Potential Research Articles

Unveiling the broad spectrum efficacy of volatile terpenes to fight against SARS-COV-2-associated mucormycosis.

Mucormycosis, a life-threatening fungal infection caused by Mucorales, affects immunocompromised patients, especially SARS-CoV-2 ones. Existing antifungal therapies, like amphotericin B, have serious health risks. The current study reviews the literature regarding an overview of SARS-CoV-2-associated mucormycosis, along with different terpenes from diverse edible sources such as basil, ginger, and clove, which are detected till June 2024. The antifungal potential of collected terpenes, their classifications, mechanisms of action, MIC values, and future perspectives are discussed here. The search identified 89 fungicidal volatile terpenes, belonging to about 26 families, from which 45 were selected for further in silico analysis. The results highlighted Oryzalexins B (60), Oryzalexins D (62), Carvacrol (4), Mansorin B (66), Muzigadial (86) and Lubimin (80) as potential antifungal agents against lanosterol-14-α-demethylase, CotH3 and mucoricin as potential targets in Mucorales. CotH3 is crucial for activating GRP-78, a host co-receptor for ACE2, essential for SARS-CoV-2 pathogenesis. Additionally, carvacrol was in vitro investigated against Mucor racemosus via the agar diffusion method, giving an MIC value of 1 mg/ml, compared to 0.1 mg/ml of ketoconazole. This study suggests promising potential for volatile terpenes in combating SARS-CoV-2-associated mucormycosis, with the need for further refined in vitro and in vivo studies to establish clinical efficacy.

Synthesis, X-Ray Structure, Characterization, Antifungal Activity, DFT, and Molecular Simulation of a Novel Pyrazole Carboxylic Acid.

The search for new antifungal agents is critical due to the rising resistance of fungal pathogens to existing treatments. This study focuses on the synthesis and evaluation of a novel compound, 1-benzyl-5-methyl-1H-pyrazole-3-carboxylic acid (compound L1), as a potential antifungal agent. Compound L1 was synthesized and characterized using a range of analytical techniques, including 1H^1H1H NMR, 13C^{13}C13C NMR, FT-IR, GC-MS, and X-ray single crystal diffraction (XRD). The antifungal activity of the compound was assessed in vitro, and its molecular structure was studied using Density Functional Theory (DFT). Molecular docking and dynamics simulations were conducted to evaluate the interaction of the compound with sterol 14-alpha demethylase (CYP51) from Candida albicans. ADME/Tox evaluations were also performed to assess the drug-like properties of compound L1. Compound L1 exhibited moderate antifungal activity with an IC50 value of 34.25 μg/mL. DFT studies confirmed the highly stable molecular structure of the compound. Molecular docking and dynamics simulations demonstrated that compound L1 had a higher affinity and stability when forming complexes with the crystal structure of CYP51, particularly in interaction with the tetrazole- based antifungal drug candidate VT1161 (PDB ID: 5TZ1). ADME/Tox evaluations indicated favorable drug-like properties for compound L1. The results suggest that compound L1 is a promising antifungal candidate, showing greater potential than fluconazole in the conducted evaluations. Further studies are warranted to explore its full therapeutic potential.

Synthesis and evaluation of the antifungal and antibiofilm potential of aminochalcones.

Candida is a commensal fungus of clinical interest that commonly lives in oral cavity and intestine but can become an opportunist microrganism and cause severe infections. A serie of 10 aminochalcones were designed and synthetized to obtain compounds anti-Candida with potent and broad-spectrum activity. The most active compound J34 demonstrated excellent in vitro activity against Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata and Candida krusei with minimum inhibitory concentration between 1.9 and 7.8µg/mL. The association of aminochalcone J34 with amphotericin B demonstrated synergistic effect against C. albicans, with Fractional Inhibiroty Concentration Index (FICI) value of 0.5. Subinhibitory concentration of J34 inhibited the C. albicans adhesion to human keratinocytes. Treatment with J34 reduced C. albicans biofilm formation, as well as acts on preformed biofilm in concentration-dependent mode. Time-kill curve demonstrated that J34 had fungicidal action after 12h of treatment. Preliminary mechanism of action study showed J34 interacts with membrane ergosterol but does not act on fungal cell wall of C. albicans. In additon, in vivo studies using Galleria mellonella indicated low toxic effect of chalcone J34 after 72h of treatment.

Antifungal Potential of Biogenic Zinc Oxide Nanoparticles for Controlling Cercospora Leaf Spot in Mung Bean.

Agricultural growers worldwide face significant challenges in promoting plant growth. This research introduces a green strategy utilizing nanomaterials to enhance crop production. While high concentrations of nanomaterials are known to be hazardous to plants, this study demonstrates that low doses of biologically synthesized zinc oxide nanoparticles (ZnO NPs) can serve as an effective regulatory tool to boost plant growth. These nanoparticles were produced using Nigella sativa seed extract and characterized through UV-Vis spectroscopy, FT-IR, X-ray diffraction, and scanning electron microscopy (SEM). The antifungal properties of ZnO NPs were evaluated against Cercospora canescens, the causative agent of Cercospora leaf spot in mung bean. Application of ZnO NPs significantly improved plant metrics, including shoot, root, pod, leaf, and root nodule counts, as well as plant length, fresh weight, and dry weight-all indicators of healthy growth. Moreover, low-dose ZnO NPs positively influenced enzymatic activity, physicochemical properties, and photosynthetic parameters. These findings suggest that biologically synthesized ZnO NPs offer a promising approach for enhancing crop yield and accelerating plant growth.

Humanized Candida and NanoBiT Assays Expedite Discovery of Bdf1 Bromodomain Inhibitors With Antifungal Potential.

The fungal Bromodomain and Extra-Terminal (BET) protein Bdf1 is a potential antifungal target against invasive fungal infections. However, the need to selectively inhibit both Bdf1 bromodomains (BDs) over human orthologs and the lack of molecular tools to assess on-target antifungal efficacy hamper efforts to develop Bdf1 BD inhibitors as antifungal therapeutics. This study reports a phenyltriazine compound that inhibits both Bdf1 BDs from the human fungal pathogen Candida glabrata with selectivity over the orthologous BDs from the human BET protein Brd4. On-target antifungal activity is established by devising two yeast-based inhibition assays: a growth assay using humanized Candida strains in which the Bdf1 BDs are replaced by their Brd4 counterparts, and a NanoBiT assay that evaluates the BD-mediated association of Bdf1 with chromatin. These assays additionally enable the discovery that BET inhibitor I-BET726 targets both Bdf1 BDs, inhibits the growth of a broad spectrum of Candida species, including antifungal-resistant clinical isolates, and displays efficacy in an invertebrate animal model of infection. These collective findings highlight the promising potential of Bdf1 BD inhibitors as an innovative class of antifungal therapeutics and the pivotal role of yeast-based assay development toward achieving this end.

Tropical fruit-derived Lactiplantibacillus as potential probiotic and antifungal agents against Fusarium oxysporum

Fifty-five lactic acid bacteria (LAB) were isolated from seven selected tropical fruits, with Solanum nigrum exhibiting the highest LAB prevalence and Couroupita guianenis and Musa fruits showing the lowest counts. Two strains isolated from Ficus racemosa demonstrated significant antifungal activity against Fusarium oxysporum. 16S rDNA sequencing identified these strains as Lactiplantibacillus plantarum MYSVCF3 and Lpb. argentoratensis MYSVCF5. The isolates displayed adaptability to a broad range of environmental conditions, including temperatures of 10–45 °C, pH 2–6, and salt up to 7%. The strains tolerated simulated gastrointestinal conditions of acid (pH-2), phenol (0.6%), and bile (0.3%) suggesting potential probiotic attributes. Lpb. argentoratensis MYSVCF5 inhibited F. oxysporum, two ESKAPE group bacteria (P. aeruginosa, S. aureus) plus S. paratyphi and E. coli. The cell-free supernatant (CFS) of Lpb. argentoratensis MYSVCF5 reduced the growth of fungal biomass by 94% and completely inhibited conidial germination, retaining activity even after extended cold storage. LC–MS/MS analysis identified organic acids in the CFS, with citric acid as the most abundant at 34.9 (± 0.3) µg/mL, followed by lactic (8.3 µg/mL) and malic acids (5.2 µg/mL). This study isolated a novel LAB, a potential candidate having probiotics and antifungal properties for application in food and agriculture.

FORMULATION OF TOLNOFTATE LOADED CUBOSOMES FOR EFFECTIVE TRANSDERMAL DELIVERY: AN IN VITRO AND EX-VIVO STUDY

Objective: The novel topical application has several benefits over traditional dosing forms, such as preventing gastrointestinal discomfort, lowering liver drug metabolism, and increasing medication bioavailability. Tolnaftate is used as potential anti-fungal agent various fungal infections. Methods: The cubosomes were formulated by emulsification technique using probe sonicator. The formulation was optimized using different concentrations of glyceryl monooleate and poloxamer 407. Results: The formed cubosomes dispersion was subjected to entrapment efficiency, surface morphology, particle size, in vitro release, anti-fungal study and ex-vivo study. The improved formulation was then transformed to a cubosomal hydrogel by the addition of carbopol 934. The average particle size of the optimised cubosomes was 208.0 nm. Zeta potential has been found to be 49.8 mV, with an entrapment efficiency of almost 90.0%. The drug steady-state flux (Jss) values for Tolnaftate Cubosomal formulation, marketed formulation, and plain drug gel were nearly 11.98, 10.23, and 10.06 g/cm2. h. As compared to standard marketed preparation, the cubosome-loaded formulation demonstrated enhanced penetration, extended deposition, and prolonged drug release. Conclusion: The drug had low solubility and permeability; it was overcome and produced superior outcomes in the form of cubosomes, which considerably increased the drug's solubility and permeability.

Anti-furfurative comparison of Kesh Kanti-Herbal Shampoos and synthetic shampoos against Malassezia furfur for dandruff management

Malassezia furfur is the primary etiological agent of dandruff (Pityriasis capitis). Although herbal shampoos are preferred for their natural, mild ingredients over synthetic counterparts, they are often perceived as less effective in managing flaky scalp conditions or furfuration causing dandruff. The study compares the antifungal efficacy of herbal and synthetic shampoos against M. furfur. Seven shampoos including herbal (HS_Adv, HS_M&P, HS_Aloe), synthetic (SYN_01, SYN_02, SYN_03) and an antifungal shampoo containing ketoconazole (KETO) were employed in the study. Experiments were designed to stimulate real-world conditions, utilizing disc-diffusion assay, 3-minute shampoo contact at mild dilutions (1% and 5%), recurrent 3-minute shampoo contact every 24 h with intermittent recovery. Both disc diffusion and 3-minute shampoo contact demonstrated that all shampoos were effectively inhibiting the viability of M. furfur. However, a single 3-minute shampoo contact followed by a prolonged recovery of 72 h revealed SYN_01 and KETO with maximal antifungal action. In contrast, herbal shampoos were as effective as synthetic options when M. furfur was subjected to 3-minute shampoo contact every 24 h with intermittent recovery. Comprehensive ingredient analysis revealed the robust antifungal activity in SYN_01 was probably because of the presence of various surfactants, allergens and a potent synthetic antifungal agent, Piroctone olamine. This study experimentally demonstrates that herbal shampoos are as effective as synthetic options in managing M. furfur-induced dandruff when applied consistently. The findings highlight the importance of regular scalp cleansing for dandruff management and provide valuable insights into the antifungal potential of both herbal and synthetic formulations.

Carbon dots as smart biosensing and imaging materials delving with antimicrobial, antifungal, and antiviral potentials against infectious pathogens

AbstractIn the emerging era of infectious diseases, antimicrobials are widely applied against pathogenic microbes (i.e., bacteria, fungus, or virus) to avoid global mortality. Nonetheless, quite a few of the microbiome adopted genetic mutations over extended period and fostered sustainable resistance towards the existing and newer antibiotics. Carbon dots (CDs) are the carbon‐based nanomaterials, unveiled their potential as antifungal, antibacterial, and antiviral agents resembled with ease of synthesis, reduced toxicity, smart functionalization, high aqueous dispersibility, and auspicious biocompatibility. This review has emphasized over the discussion corroborated with the types of CDs and their synthesis, and numerous properties of CDs tailored to their biofunctionalization. Further the article was featured with the antibacterial, antiviral, antifungal, bioimaging, biosensing, and anticancer responsiveness of CDs (in vivo and in vitro mode) followed by their biocompatibility, toxicity assessments, challenges, and future prospectives.

Chemical characterization of Eucalyptus (Eucalyptus globulus) leaf essential oil and evaluation of its antifungal, antibacterial and antioxidant activities.

This study investigates the chemical composition of the essential oil (EO) extracted by hydrodistillation from dry Eucalyptus leaves (Eucalyptus globulus) and its antifungal, antibacterial and antioxidant potential. The Eucalyptus leaves were harvested in the commune of Seraïdi (north-eastern Algeria). Chemical analysis carried out by chromatography coupled with mass spectrophotometry (GC-SM) revealed the presence of 20 molecules representing approximately 100% of the overall component, with a yield of 1.58%. This oil is composed mainly of linalool (30.09%), followed by b-Linalyl oxide (13.93%), Camphor (12.09%), 1,8-Cineole=eucalyptol (10.95%) and Bergamol (10.03%). Other constituents were identified at relatively medium (Epoxylinalol - 8.82%, Borneol - 5.71%) and low (alpha-Terpinol - 1.11) levels. This result shows that this EO differs from those usually extracted from eucalyptus leaves because it is of linalool chemotype and not eucalyptol. The determination of the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) was carried out to evaluate the antifungal activity of Eucalyptus EO on the growth of Fusarium roseum mycelium. The values recorded are 2500µg/ml for the MIC and 4000µg/ml for the MFC. The results obtained revealed an antifungal activity of this oil for practically all doses applied against Fusarium mycelial proliferation despite the low reported levels of 1,8-cineole compared to the other components. The antibacterial activity against the Pseudomonas savastanoi strain was also examined which revealed effectiveness of this oil. In parallel, the DPPH test revealed a moderate antioxidant activity of the studied EO compared to Vit C with an IC50 17mg/ml probably due to its components' antagonistic or synergistic effect.

Discovery of novel flavonoid derivatives containing benzothiazole as potential antifungal agents.

Fungal diseases of plants have a serious impact on the quality and yield of crops, and some traditional pesticides can no longer cope with this problem. Therefore, it is of great significance to develop new pesticides with high efficiency and low toxicity. A series of flavonoid derivatives containing benzothiazole were designed and synthesized. Among them, the compounds V17, V12, and V13 had excellent inhibitory effect against Fusarium oxysporum f. sp. cucumerinu with the half-maximal effect concentration (EC50) values of 1.2, 2.3, and 3.2 μg/mL, which were better than the control drug Kresoxim-methyl (Km, 37.8 μg/mL). The in vivo protective activity and curative activities of V17 against cucumber fusarium wilt caused by F. oxysporum f. sp. cucumerinum were 82.4 and 60.5% at 200 μg/mL, better than Km (60.2 and 48.6%). In addition, V17 could damage the cell membrane of the mycelia, which can be confirmed by determination of cytoplasmic leakage, detection of cell membrane permeability, and measurement of malondialdehyde (MDA). Similarly, the scanning electron microscopy (SEM) experiment and optical microscope characterization provide direct evidence for destruction of mycelium treated with V17. V17 significantly reduced the pathogenicity of the F. oxysporum f. sp. cucumerinum, which provided a new idea and direction for the development of green pesticides. © 2025 Society of Chemical Industry.

Evaluating the Role of Viable Cells, Heat-Killed Cells or Cell-Free Supernatants in Bacterial Biocontrol of Fungi: A Comparison Between Lactic Acid Bacteria and Pseudomonas.

This study investigated whether viable cells, dead cells or cell-free supernatants (CFS) were responsible for the biocontrol effect of strains from two important bacterial genera, Pseudomonas and Lactobacillus, known for their antifungal properties against plant pathogens and food spoilage microorganisms. Specifically, the capability of these strains to produce extracellular hydrolytic enzymes on specified media was assessed, along with their effectiveness in inhibiting the mycelial growth of several phytopathogenic fungi (Fusarium oxysporum, Botrytis cinerea, Pythium ultimum and Rhizoctonia solani) using dual culture plate assays. Results from these inhibition assays revealed that P. fluorescens PF05 and L. plantarum LMG 23520 strains were the most effective in suppressing fungal growth, especially F. oxysporum. Therefore, further experiments were carried out to investigate the antifungal potential of the viable cells, heat-killed cells (HKC) and CFS from these strains against the germination of F. oxysporum spores. The viable cell trial proved successful, whereas HKC from the two bacterial isolates were ineffective against fungal spore germination. Conversely, the CFS of L. plantarum LMG 23520 was able to prevent fungal spore development for up to six days. The CFS of P. fluorescens PF05, instead, did not yield positive results. Additional studies are required to evaluate the potential inhibitory effects of the CFS from P. fluorescens PF05 and the HKC from both strains.

Antifungal Potentials of Asian Plants: Ethnobotanical Insights and Phytochemical Investigations.

Ethnomedicinal plants in Asia offer a promising, low-side-effect alternative to synthetic drugs for treating fungal infections, one of the most widespread communicable diseases caused by pathogenic fungi. Despite being underexplored, the region's rich plant diversity holds the potential for developing effective antifungal drugs. Research is increasingly focused on bioactive compounds from these plants, which show strong antifungal properties and may serve as leads for new drug development. This comprehensive review included 257 articles from 658 published ones, selecting only peer-reviewed, English-language studies that met the inclusion criteria. In this review, we have discussed 27 Asian medicinal plants that contain 67 responsible phytochemicals deciphering promising antifungal action. This finding revealed that Asian plant diversity can be helpful in treating fungal invasion against several fungal species. Inhibition and reduction of mycelial growth and zoospore germination, fungistatic and fungicidal activities, and inhibition of ergosterol biosynthesis are some common mechanisms reported in this review. Thus, this Asian plant diversity can provide a ray of hope as a modern therapeutic approach to bypass antimicrobial resistance issues noticed in recent days. Further research is still recommended to ascertain their exact mode of action, required dose, and safety and efficacy profile.

A study to assess the pharmacological agent potential of gold nanoparticles and their effects on human cancer cells and hospital pathogens using in vitro methods.

Interest in metal nanoparticles synthesised using green methods is growing steadily. Metal nanoparticles can be synthesised inexpensively and effortlessly using extracts derived from different plants and their diverse components. Gold nanoparticles (Au NPs) were rapidly synthesised from Broccoli (Brassica oleracea L.) agricultural waste using a novel, cost-effective, and eco-friendly method in this work. Analysed data from various techniques including UV-vi, TEM, FESEM, XRD, AFM, FTIR, TGA-DT, EDX, and DLS to assess the properties of the synthesised Au NPs. The characterisation data revealed that the Au NPs had a peak absorbance at 553.10nm, a surface charge of -19.7mV, an average hydrodynamic size of 78.75nm, a monodisperse spherical shape, and were found to be stable. The inhibitory effects of Au NPs with these properties on hospital pathogens and human cancer cells were evaluated by microdilution, disk diffusion and MTT techniquesAs a result of the findings, it was determined that Au NPs have antibacterial, antifungal and anticancer potential as pharmacological agents under in vitro conditions.

Exploring the antifungal potential of Cannabis sativa-derived stilbenoids and cannabinoids against novel targets through in silico protein interaction profiling.

Cannabinoid and stilbenoid compounds derived from Cannabis sativa were screened against eight specific fungal protein targets to identify potential antifungal agents. The proteins investigated included Glycosylphosphatidylinositol (GPI), Enolase, Mannitol-2-dehydrogenase, GMP synthase, Dihydroorotate dehydrogenase (DHODH), Heat shock protein 90 homolog (Hsp90), Chitin Synthase 2 (CaChs2), and Mannitol-1-phosphate 5-dehydrogenase (M1P5DH), all of which play crucial roles in fungal survival and pathogenicity. This research evaluates the binding affinities and interaction profiles of selected cannabinoids and stilbenoids with these eight proteins using molecular docking and molecular dynamics simulations. The ligands with the highest binding affinities were identified, and their pharmacokinetic profiles were analyzed using ADMET analysis. The results indicate that GMP synthase exhibited the highest binding affinity with Cannabistilbene I (-9.1kcal/mol), suggesting hydrophobic solid interactions and multiple hydrogen bonds. Similarly, Chitin Synthase 2 demonstrated significant binding with Cannabistilbene I (-9.1kcal/mol). In contrast, ligands such as Cannabinolic acid and 8-hydroxycannabinolic acid exhibited moderate binding affinities, underscoring the variability in interaction strengths among different proteins. Despite promising in silico results, experimental validation is necessary to confirm therapeutic potential. This research lays a crucial foundation for future studies, emphasizing the importance of evaluating binding affinities, pharmacokinetic properties, and multi-target interactions to identify promising antifungal agents.

Synthesis and Antifungal Activity of Fmoc-Protected 1,2,4-Triazolyl-α-Amino Acids and Their Dipeptides Against Aspergillus Species.

In recent years, fungal infections have emerged as a significant health concern across veterinary species, especially in livestock such as cattle, where fungal diseases can result in considerable economic losses, as well as in humans. In particular, Aspergillus species, notably Aspergillus flavus and Aspergillus versicolor, are opportunistic pathogens that pose a threat to both animals and humans. This study focuses on the synthesis and antifungal evaluation of novel 9-fluorenylmethoxycarbonyl (Fmoc)-protected 1,2,4-triazolyl-α-amino acids and their dipeptides, designed to combat fungal pathogens. More in detail, we evaluated their antifungal activity against various species, including Aspergillus versicolor (ATCC 12134) and Aspergillus flavus (ATCC 10567). The results indicated that dipeptide 7a exhibited promising antifungal activity against Aspergillus versicolor with an IC50 value of 169.94 µM, demonstrating greater potency than fluconazole, a standard treatment for fungal infections, which showed an IC50 of 254.01 µM. Notably, dipeptide 7a showed slightly enhanced antifungal efficacy compared to fluconazole also in Aspergillus flavus (IC50 176.69 µM vs. 184.64 µM), suggesting that this dipeptide might be more potent even against this strain. Remarkably, 3a and 7a are also more potent than fluconazole against A. candidus 10711. On the other hand, the protected amino acid 3a demonstrated consistent inhibition across all tested Aspergillus strains, but with an IC50 value of 267.86 µM for Aspergillus flavus, it was less potent than fluconazole (IC50 184.64 µM), still showing some potential as a good antifungal molecule. Overall, our findings indicate that the synthesized 1,2,4-triazolyl derivatives 3a and 7a hold significant promise as potential antifungal agents in treating Aspergillus-induced diseases in cattle, as well as for broader applications in human health. Our mechanistic studies based on molecular docking revealed that compounds 3a and 7a bind to the same region of the sterol 14-α demethylase as fluconazole. Given the rising concerns about antifungal resistance, these amino acid derivatives, with their unique bioactive structures, could serve as a novel class of therapeutic agents. Further research into their in vivo efficacy and safety profiles is warranted to fully realize their potential as antifungal drugs in clinical and agricultural settings.

The Use of Specific Non-Saccharomyces Yeasts as Sustainable Biocontrol Solutions Against Botrytis cinerea on Apples and Strawberries.

Apples and strawberries hold significant commercial and nutritional value but face pre- and post-harvest spoilage due to infections by Botrytis cinerea. While spoilage is conventionally managed using synthetic chemicals, there is a growing interest in utilising yeasts as biological control agents. This study aimed to assess the antifungal potential of non-Saccharomyces yeasts Suhomyces pyralidae, Meyerozyma guilliermondii, Pichia kluyveri, Zygoascus hellenicus, and Aureobasidium melanogenum against three B. cinerea strains (B05.10, IWBT-FF1, and PPRI 30807) on agar plates and in post-harvest trials on apples and strawberries. Aureobasidium melanogenum exhibited a broad range of extracellular enzyme production and inhibition rates of 55%, 52%, and 40% against the strains. In volatile organic compound (VOC) assays, P. kluyveri and S. pyralidae achieved 79% and 56% inhibition, respectively, with VOCs like isobutanol, isoamyl alcohol, 2-phenylethanol, isoamyl acetate, and 2-phenethyl acetate identified. In post-harvest trials, S. pyralidae was most effective on apples, with inhibition rates up to of 64%. The commercial fungicide Captan and S. pyralidae and P. kluyveri achieved 100% inhibition against the B. cinerea strains B05.10 and IWBT-FF1 on strawberries. These findings highlight the potential of the selected yeast species as biological control agents against B. cinerea, warranting further research into their application in commercial fruit protection.

Unveiling the cyclopropyl appended acyl thiourea derivatives as antimicrobial, α-amylase and proteinase K inhibitors: Design, synthesis, biological evaluation, molecular docking, DFT and ADMET studies.

Acyl thiourea scaffolds are frequently employed in drug development to discern unique and essential therapies for the eradication of the most challenging diseases. Hence, we developed a library of novel cyclopropyl incorporating acyl thiourea derivatives (4a-j) and evaluated their antimicrobial, α-amylase, and proteinase K inhibition potential. Compound (4h) (4-methoxy) demonstrated the strongest α-amylase inhibition (IC50=1.572±0.017 μM), while compound (4j) (3,4,5-trimethoxy) exhibited potent proteinase K inhibition (IC50 = 1.718±0.061μM), comparable to the standard acarbose (IC50=1.063±0.013μM) and phenyl methyl sulfonyl fluoride (IC50=0.119±0.014μM). The unsubstituted compound (4a) emerged as the most potent antifungal agent (17mm zone of inhibition), outperforming the positive control Terbinafine (zone of inhibition 16mm). These compounds (4a-j) also displayed moderate antibacterial activity. SAR analysis revealed the influences of various substitutions on the acyl thiourea scaffold. Computational studies, including DFT, molecular docking, and ADMET predictions, supported the biological findings and identified these compounds as promising inhibitors of α-amylase, proteinase K, and microbial pathogens.

Acrylpimaric acid-modified chitosan derivatives as potential antifungal agents against Valsa Mali.

In order to the antifungal activity of chitosan (CS) and to obtain a better natural bio-antimicrobial agent, CS was modified with acrylpimaric acid (APA). The grafting sites of APA on CS were controlled by adjusting the reaction time and the ratio of reactants to obtain APA grafted with CS C2-NH2 (NCSAA) and C6-OH (CSAA). Intermediates to protect C2-NH2 (PMCSAA) and final sample derivatives (PCSAA) were prepared using phthalic anhydride. The structural and crystal variations of the four derivatives were analyzed and determined by FTIR, 1H NMR and XRD. The in vitro antifungal activities of the four modified samples against V. mali, C. lunata, A. solani, F. oxysporum f. sp. niveum, and F. graminearum were evaluated by the mycelial growth rate method, and PCSAA was screened for optimal inhibitory effect on V. mali with an EC50=38.66μg/mL. The SEM and TEM showed that these derivatives cause the loss of mycelial contents by disrupting the ultrastructure of the mycelium, destroying the internal structure of the mycelium, and preventing the cells from carrying out their normal life activities. In vivo experiments showed better curative effect (79.09%±2.00) and protective effect (80.93%±0.03) of PCSAA at 200μg/mL.

Synthesis, characterization and biological profile of some new dihydropyrimidinone derivaties.

The rise of drug-resistant bacteria, viruses, and fungi has prompted the search for new drugs without cross-resistance to current treatments. As a result, the aim of this research was to synthesize various types of dihydropyrimidinones heterocyclic compounds and screened them for their antibiotic properties. Newly synthesized dihydropyrimidinone derivatives were characterized spectroscopically using proton NMR (1HNMR), and FT-IR. These substances were then subjected to molecular docking studies via Auto dock Vina software to determine their affinity for binding to proteins from different bacterial strains including (Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), Mycobacterium luteus (M. luteus), Salmonella typhi (S.typhi), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli) and fungal (Candida glabrata (C. glabrata), Candida albicans (C. albicans), and Saccharomyces cerevisiae (S. cerevisiae) strains. Also in-vitro anti-fungal, anti-bacterial and anti-oxidant activity was performed by using ager well diffusion method and DPPH assay respectively. Moreover, the In-vivo biological evaluation of these derivatives was conducted by using carrageenan-induced hind paw model. The cytotoxicity profile of the synthesized derivatives was done via in-vitro MTT assay. All newly synthesized derivatives were confirmed via the multiple spectroscopic analysis techniques. All derivatives showed good binding affinities against the multiple targeted protein with. Compound 4c exhibited hightest potential with -10kcal/mol against bacterial strains. 4b showed best antifungal potential with -10.8kcal/mol binding affinities. For Bacillus subtilis compound 4b and 4c performed best with 17mm±2.21. for anti-fungal activity against Candida glabrata, amongst the five newly formed compounds, 4a showed best activity with 19mm±1.22 The analogue 4b exhibited best anti-oxidant potential with 63.85±1.39. Compound 4a and 4b showed highest anti-inflammatory potential with 1.011mm±0.247mg/kg and 1.447±0.212mg/kg in countering inflammation by targeting toll-like receptor activation and reduce the inflammation in hind paw edema. The selected derivatives exhibited no toxicity profile with 99 % and 98 % cell survival rate using compound 4a and 4b. Research has been done on the multiple biological activities of dihydropyrimidinones derivatives but the innovation on MDR is still pending. New dihydropyrimidinone derivatives were developed as agents to combat drug resistance. The results of these studies showed that newly synthesized dihydropyrimidinone derivatives are remarkably effective not only as anti-biotic agents but also counter inflammation caused by carrageenan resulting from the activation of the Toll-like receptors (TLRs) signaling pathway along with the non-toxic effect. So it is concluded that the recently synthesized new dihyropyrimidinone derivatives are highly effective antimicrobial derivatives with non-toxic effects on human cell lines.