anti-Candida Agents Research Articles

Evaluation of antifungal and apoptotic effects of linalool, citral, and carvacrol separately and in combination with nystatin against clinical isolates of Pichia kudriavzevii

Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains.Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells.Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections.

Mapping of the Lipid-Binding Regions of the Antifungal Protein NFAP2 by Exploiting Model Membranes.

Fungal infections with high mortality rates represent an increasing health risk. The Neosartorya (Aspergillus) fischeri antifungal protein 2 (NFAP2) is a small, cysteine-rich, cationic protein exhibiting potent anti-Candida activity. As the underlying mechanism, pore formation has been demonstrated; however, molecular level details on its membrane disruption action are lacking. Herein, we addressed the lipid binding of NFAP2 using a combined computational and experimental approach to simple lipid compositions with various surface charge properties. Simulation results revealed binding preferences for negatively charged model membranes, where selectivity is mediated by anionic lipid components enriched at the protein binding site but also assisted by zwitterionic lipid species. Several potential binding routes initiated by various anchoring contacts were observed, which resulted in one main binding mode and a few variants, with NFAP2 residing on the membrane surface. Region 10NCPNNCKHKKG20 of the flexible N-terminal part of the protein showed potency to insert into the lipid bilayer, where the disulfide bond-stabilized short motif 11CPNNC15 could play a key role. In addition, several areas, including the beginning of the N-terminal (residues 1-8), played roles in facilitating initial membrane contacts. Besides, individual roles of residues such as Lys24, Lys32, Lys34, and Trp42 were also revealed by the simulations. Combined data demonstrated that the solution conformation was not perturbed markedly upon membrane interaction, and the folded part of the protein also contributed to stabilizing the bound state. Data also highlighted that the binding of NFAP2 to lipid vesicles is sensitively affected by environmental factors such as ionic strength. Electrostatic interactions driven by anionic lipids were found pivotal, explaining the reduced membrane activity observed under high salt conditions. Experimental data supported the lipid-selective binding mechanisms and pointed to salt-dependent effects, particularly to protein-assisted vesicle aggregation at low ionic strength. Our findings can contribute to the development of NFAP2-based anti-Candida agents and studies aiming at future medical use of peptide-based natural antifungal compounds.

Anticandidal applications of selenium nanoparticles biosynthesized with Limosilactobacillus fermentum (OR553490)

Candida albicans is one of the most dangerous pathogenic fungi in the world, according to the classification of the World Health Organization, due to the continued development of its resistance to currently available anticandidal agents. To overcome this problem, the current work provided a simple, one-step, cost-effective, and safe technique for the biosynthesis of new functionalized anticandidal selenium nanoparticles (Se NPs) against C. albicans ATCC10231 using the cell-free supernatant of Limosilactobacillus fermentum (OR553490) strain. The bacterial strain was isolated from yogurt samples available in supermarkets, in Damietta, Egypt. The mixing ratio of 1:9 v/v% between cell-free bacterial metabolites and sodium selenite (5 mM) for 72 h at 37 °C were the optimum conditions for Se NPs biosynthesis. Ultraviolet–visible spectroscopy (UV–Vis), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), Zeta analyses, and elemental analysis system (EDS) were used to evaluate the optimized Se NPs. The Se NPs absorption peak appeared at 254 nm. Physicochemical analysis of Se NPs revealed the crystalline-shaped and well-dispersed formation of NPs with an average particle size of 17–30 nm. Se NPs have − 11.8 mV, as seen by the zeta potential graph. FT-IR spectrum displayed bands of symmetric and asymmetric amines at 3279.36 cm−1 and 2928.38 cm−1, aromatic and aliphatic (C–N) at 1393.32 cm−1 and 1237.11.37 cm−1 confirming the presence of proteins as stabilizing and capping agents. Se NPs acted as a superior inhibitor of C. albicans with an inhibition zone of 26 ± 0.03 mm and MIC value of 15 µg/mL compared to one of the traditional anticandidal agent, miconazole, which revealed 18 ± 0.14 mm and 75 µg/mL. The cytotoxicity test shows that Se NPs have a low toxic effect on the normal keratinocyte (IC50 ≈ 41.5 μg/mL). The results indicate that this green synthesis of Se NPs may have a promising potential to provide a new strategy for drug therapy.

Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis.

Currently, the spread of fungal infections is becoming an urgent problem. Fungi of the Candida genus are opportunistic microorganisms that cause superficial and life-threatening systemic candidiasis in immunocompromised patients. The list of antifungal drugs for the treatment of candidiasis is very limited, while the prevalence of resistant strains is growing rapidly. Therefore, the search for new antimycotics, including those exhibiting immunomodulatory properties, is of great importance. Plenty of natural compounds with antifungal activities may be extremely useful in solving this problem. This review evaluates the features of natural antimicrobial peptides, namely plant defensins as possible prototypes of new anticandidal agents. Plant defensins are important components of the innate immune system, which provides the first line of defense against pathogens. The introduction presents a brief summary regarding pathogenic Candida species, the pathogenesis of candidiasis, and the mechanisms of antimycotic resistance. Then, the structural features of plant defensins, their anticandidal activities, their mechanisms of action on yeast-like fungi, their ability to prevent adhesion and biofilm formation, and their combined action with conventional antimycotics are described. The possible mechanisms of fungal resistance to plant defensins, their cytotoxic activity, and their effectiveness in in vivo experiments are also discussed. In addition, for the first time for plant defensins, knowledge about their immunomodulatory effects is also presented.

Novel aza-bicyclic 2-isoxazoline acylhydrazone hybrids and their synergistic potential with fluconazole against a drug-resistant Candida albicans strain.

As the prevalence of drug-resistant Candida isolates continues to rise, the imperative for identifying novel compounds to enhance the arsenal of antifungal drugs becomes increasingly critical. Consequently, exploring new treatment strategies, including synthesizing molecular hybrids and applying combination therapy, is essential. For this reason, this study evaluated the efficacy of ten molecular hybrids of aza-bicyclic 2-isoxazoline-acylhydrazone belonging to two series 90 and 91 as possible anti-Candida agents. In addition, we also investigated the interaction between the hybrids and fluconazole, a commonly used antifungal drug. We evaluated the antifungal effect of aza-bicyclic 2-isoxazoline-acylhydrazone hybrid compounds against six Candida spp. strains that target planktonic cells. However, none of these new molecules were inhibitory active at the tested concentrations (2 to 1,024µg/mL). Moreover, we analyzed the interaction between the ten new hybrid molecules and fluconazole using the checkerboard assay, employing two different methodologies for reading the plate. For this, one isolate fluconazole-resistant was selected. We observed that only one combination, 6-(4-tert-butylbenzoil)-4,5,6,6a-tetrahydro-3a-H-pirrole[3,2-d]isoxazole-3-carboxylic(furan-2-metilidene)-hydrazide (91e) and fluconazole, exhibited a synergistic interaction (FICI range 0.0781 to 0.4739). The combination successfully inhibited the growth of C. albicans CA2 fluconazole-resistant, and no interaction was observed in an isolate susceptible to fluconazole. Additionally, these results emphasize the continued need for research into new compounds and the importance of using combined approaches to increase their activity.

Silver(I) complexes with voriconazole as promising anti-Candida agents

Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV–Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(H2O)]CH3SO3}n (1), {[Ag(vcz)2]BF4}n (2) and {[Ag(vcz)2]PF6}n (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry. On the other hand, DFT calculations revealed that the investigated silver(I) complexes 1–3 in DMSO exist as linear [Ag(vcz-N2)(vcz-N19)]+ (1a), [Ag(vcz-N2)(vcz-N4)]+ (2a) and [Ag(vcz-N4)2]+ (3a) species, respectively. The evaluated complexes showed an enhanced anti-Candida activity compared to the parent drug with minimal inhibitory concentration (MIC) values in the range of 0.02–1.05 μM. In comparison with vcz, the corresponding silver(I) complexes showed better activity in prevention hyphae and biofilm formation of C. albicans, indicating that they could be considered as promising agents against Candida that significantly inhibit its virulence. Also, these complexes are much better inhibitors of ergosterol synthesis in the cell membrane of C. albicans at the concentration of 0.5 × MIC. This is also confirmed by a molecular docking, which revealed that complexes 1a – 3a showed better inhibitory activity than vcz against the sterol 14α-demethylase enzyme cytochrome P450 (CYP51B), which plays a crucial role in the formation of ergosterol.

Synthesis of bio-stabilized silver nanoparticles using Roccella montagnei, their anticandidal capacities & potential to inhibit the virulence factors in fluconazole-resistant Candida albicans.

Candida species is the causative agent in approximately 80% of invasive mycoses and drug-resistant Candida albicans is among the four strains of 'critical priority group' framed by WHO. Lichens are endowed with some rare phytochemicals and a plethora of therapeutics viz. antifungal capacities of Roccella montagnei. Biosynthesis of silver nanoparticles (AgNPs) using lichen could offer an eco-friendly, and cost-effective alternative against emerging 'microbial resistance.' Therefore, the objective was to biosynthesize silver nanoparticles (Rm-AgNPs) using a Hydro-alcoholic (1:1) extract of R. montagnei to develop a potent anticandidal agent against Fluconazole-resistant C. albicans NBC099. UV-Spectroscopy identified AgNPs specific-peak of Rm-AgNPs at 420-440nm and FTIR revealed the presence of amines, alcohol, aromatic compounds, and acids. SEM and TEM analysis indicated that Rm-AgNPs are spherical shaped with a size range of 10-50nm. Zetasizer analysis indicated that particles are highly stable and have a mean hydrodynamic diameter of 116nm with a zeta potential charge of - 41mV. XRD analysis suggested face centered cubic crystal lattice structure. Results indicated that Rm-AgNPs strongly inhibited the growth of NBC099 at a minimum inhibitory concentration (IC50) of ≤ 15µg. C. albicans culture treated with Rm-AgNPs at concentrations below IC50, down-regulates the production of different virulence factors in NBC099, viz. hyphal formation (> 85%), biofilms production (> 80%), phospholipase, esterase, proteinase activity. The apoptosis assay demonstrated the Rm-AgNPs induced apoptosis in NBC099 cells via oxidative stress. Interestingly, Rm-AgNPs showed negligible cytotoxicity (< 6%) in murine RAW 246.7 macrophage cells at a concentration above 15µg/mL. Therefore, Rm-AgNPs have been offered as an anti-candida alternative that can be utilized to improve the efficacy of already available medications.

Synthesis, structure–activity relationship and biological evaluation of indole derivatives as anti-Candida albicans agents

In this work, we synthesized a series of indole derivatives to cope with the current increasing fungal infections caused by drug-resistant Candida albicans. All compounds were evaluated for antifungal activities against Candida albicans in vitro, and the structure–activity relationships (SARs) were analyzed. The results indicated that indole derivatives used either alone or in combination with fluconazole showed good activities against fluconazole-resistant Candida albicans. Further mechanisms studies demonstrated that compound 1 could inhibit yeast-to-hypha transition and biofilm formation of Candida albicans, increase the activity of the efflux pump, the damage of mitochondrial function, and the decrease of intracellular ATP content. In vivo studies, further proved the anti-Candida albicans activity of compound 1 by histological observation. Therefore, compound 1 could be considered as a novel antifungal agent.

Antibacterial and Anticandidal Activity of the Nanostructural Composite of a Spirothiazolidine-Derivative Assembled on Silver Nanoparticles.

Our aims in this work are the preparation of an ionic liquid based on heterocyclic compounds with Ag nanoparticles and the investigation of its application as an antibacterial and anticandidal agent. These goals were achieved through the fabrication of an ionic liquid based on Ag nanoparticles with 5-Amino-3-(4-fluorophenyl)-N-hexadecyl-7-(4-methylphenyl)-2-H spiro[cyclohexane1,2'-[1,3]thiazolo [4,5-b]pyridine]-6-carbonitrile (P16). The nanostructure of the prepared ionic liquid was characterized using techniques such as FTIR, 1HNMR, 13CNMR, UV, SEM, and TEM. The biological activity of the prepared compound (P16) and its nanocomposites with Ag nanoparticles was tested using five clinical bacteria (Pseudomonas aeruginosa 249; Escherichia coli 141; Enterobacter cloacae 235; Staphylococcus epidermidis BC 161, and methicillin-resistant S. aureus 217), and three Candida species (Candida utilis ATCC 9255; C. tropicalis ATCC 1362, and C. albicans ATCC 20402). The FTIR, 1HNMR, and 13CNMR results confirmed the chemical structure of the synthesized P16 compound. The nanostructure of the prepared ionic liquid was determined based on data obtained from the UV, SEM, and TEM tests. The antibacterial and anticandidal results showed that the biological activity of the compound (P16) was enhanced after the formation of nanocomposite structures with Ag nanoparticles. Moreover, the biological activity of the compound itself (P16) and that of its nanocomposite structure with Ag nanoparticles was higher than that of ampicillin and amphotericin B, which were used as control drugs in this work.

Chitosan encapsulation of fluconazole-loaded MgO/CuO nanocomposite for biofilm inhibition of contact lens

Candidal colonization and biofilm development is the primary cause of contact lens associated keratomycosis. Protracted therapeutic courses and high doses of anticandidal agents have made treatment of the condition a challenge. The development of novel strategies to prepare non-toxic antibiofilm coating materials is required to ensure user safety and reduce unnecessary health burdens. The present study focused on the synthesis of chitosan encapsulated fluconazole loaded MgO/CuO nanocomposite from an aqueous extract of Talaromyces pupureogenus fungus isolated from the plant. T. pupureogenus extract revealed the presence of Palmitic acid, Ethanol, 1-propanol, and Trichloromethane via Gas Chromatography-mass Spectrometry (GC-MS). The presence of palmitic acid had a role as a bio-reducer and capping agent. Nanocomposites were characterized by UV–vis spectroscopy, X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Dynamic Light Scattering (DLS). Mycosynthesized nanomaterials displayed crystalline structures by XRD. FESEM analysis revealed 2D nanosheets and induction of copper with a size range of 12–24 nm in MgO/CuO nanocomposite. Minimum Inhibitory Concentration (MIC) of mycosynthesized nanomaterials depicted their low concentration that varies from 0.1 μg/ml to 10 μg/ml for anticandidal activity against the clinical strain of C.albicans whereas dose-dependent anticandidal activity by MgO/CuO nanocomposite was observed with an increase in inhibition regions. Antibiofilm analysis of synthesized nanocomposites in microtiter plates, on glass slides, on contact lenses, and contact lens cases exhibited prominent results. Biofilm inhibition by FLC-CS/MgO/CuO nanocomposite was observed as 88% indicating that chitosan encapsulated fluconazole loaded MgO/CuO nanocomposite can be used as an effective antibiofilm treatment option for contact lens associated keratomycosis. Hemolysis assay showed that Flc-CS/MgO/CuO nanocomposite are highly hemocompatible.Hence, these mycosynthesized nanocomposites are envisaged as promising materials for contact lens associated infections.

Chemically engineered nano selective silver shapes: Novel synthesis and their potential activity as anti-candida agents

Oral candidiasis (OC) is an infection of oral mucosa caused by fungal overgrowth, especially Candida albicans due to its ability to form biofilms and the increased expression of virulence factors. In the present study, Ag Nano sphere & Ag Nano triangle were newly synthesized using Juniperus drupacea L leaves extract to combat the OC infections. Ag Nano sphere & Ag Nano triangle antifungal activity, mechanism of action against OC, and cytotoxic effect in L929 (ATCC CCL-1 NCTC) fibroblast cell monolayers were evaluated. The J. drupacea phytochemical analysis revealed the presence of three major compounds: α-pinene (34.27 %), thymol methylether (15.20 %) and camphor (9.01 %). The proposed synthesis approach includes the reduction of Ag+ by Juniperus drupacea L leaves extract to form Ag Nano spheres. One the other hand, the presence of polyvinylpyrrolidone (PVP) in the reaction mixture led to obtaining Ag Nano triangle shapes. The minimal fungicidal concentration (MFC) and minimal biofilm eradication concentration (MBEC) assays revealed the higher antifungal effect of Ag Nano sphere when compared to Ag Nano triangle. MFC of Ag Nano sphere and Nano triangle reached 62.5 and 125 µg/mL respectively. While MBECs were ranged between 4 and 32 and 16–64 µg/mL upon using Ag Nano sphere and Nano triangle respectively. The possible mechanism of action of the synthesized Ag Nano shapes was the attributed to the direct effect on the cell membrane especially after 6 h incubation. In vitro cytotoxic effect of the prepared Ag-Nano sphere on cell proliferation using L929 (ATCC CCL-1 NCTC) fibroblast cell monolayers suggested the Ag-Nano spheres are safe for possible biomedical application.

In Vitro and In Vivo Anti-Candida albicans Activity of a Scorpion-Derived Peptide.

The increasing infection and drug resistance frequency has encouraged the exploration of new and effective anti-Candida albicans agents. In this study, CT-K3K7, a scorpion antimicrobial peptide derivative, effectively inhibit the growth of C. albicans. CT-K3K7 killed C. albicans cells in a dose-dependent manner, mainly by damaging the plasma membrane. CT-K3K7 could also disrupt the nucleus and interact with nucleic acid. Moreover, CT-K3K7 induced C. albicans cells necrosis via a reactive oxygen species (ROS)-related pathway. Furthermore, CT-K3K7 inhibited the hyphal and biofilm formation of C. albicans. In the mouse skin subcutaneous infection model, CT-K3K7 significantly prevented skin abscess formation and reduced the number of C. albicans cells recovered from the infection area. Taken together, CT-K3K7 has the potential to be a therapeutic for C. albicans skin infections.

Spectroscopic and in silico evaluation on the interactive behavior between substituted β-2,3-dihydrofuran naphthoquinones and human serum albumin

The interactive profile between human serum albumin (HSA, the main carrier of endogenous and exogenous compounds in the human bloodstream) and five potential anticandidal agents, namely 2,3-dihydro-2-phenyl-naphtho[1,2-b]furan-4,5‑dione (1) and its derivatives 2–5 was studied by biophysical techniques, i.e., UV–vis, circular dichroism, steady-state and time-resolved fluorescence, combined with in silico calculations. The Stern-Volmer quenching constant (KSV) trend in three different temperatures and the bimolecular quenching rate constant (kq ≈ 1012 M−1s−1) values indicated a ground-state association HSA:1–5 which was confirmed by time-resolved fluorescence decays. Both KSV and modified Stern-Volmer binding constant (Ka) values are in the order of 104 M−1, indicating a moderate binding affinity, following the same reported trend for 1,4-naphthoquinones (the isomeric form of the naphthoquinones under study). There is only one main binding site for HSA:1–5, probably the subdomain IIA where the Trp-214 residue can be found. The association is driven both enthalpically and entropically, perturbing both the microenvironment around Trp-214 residue and weakly the α-helix content of albumin. Overall, the β-2,3-dihydrofuran naphthoquinones 1–5 showed favorable binding affinity to HSA to achieve their therapeutical potential and control of effective dosages.

Similarity searching for anticandidal agents employing a repurposing approach.

Fungal infections caused by Candida are still a public health concern. Particularly, the resistance to traditional chemotherapeutic agents is a major issue that requires efforts to develop new therapies. One of the most interesting approaches to finding new active compounds is drug repurposing aided by computational methods. In this work, two databases containing anticandidal agents and drugs were studied employing cheminformatics and compared by similarity methods. The results showed 36 drugs with high similarities to some candicidals. From these drugs, trimetozin, osalmid and metochalcone were evaluated against C. albicans (18804), C. glabrata (90030), and miconazole-resistant strain C. glabrata (32554). Osalmid and metochalcone were the best, with activity in the micromolar range. These findings represent an opportunity to continue with the research on the potential antifungal application of osalmid and metochalcone as well as the design of structurally related derivatives.

Poređenje fitohemijskih svojstava, antimikrobne i antioksidativne aktivnosti etanolnih ekstrakata iz plodova crnog (Piper nigrum L.) i kubeba bibera (Piper cubeba L.) dostupnih u Srbiji

The present study aimed to compare phytochemical properties (total extractive matter, phenolic, flavonoids, and mineral content), antimicrobial and antioxidant activities of black pepper fruits' ethanolic extract (BPFEE), and cubeb pepper fruits' ethanolic extract (CPFEE). The extracts were prepared by reflux extraction under identical conditions (solvomodule 1:10 m/v, 2 h at boiling point). BPFEE had higher total phenolic and flavonoids content, lower total extractive matter and better antioxidant activity than CPFEE. Among the macroelements, the highest presence of Na was detected in both extracts in similar amounts. BPFEE contained higher amounts of K, Ca, P and Mg. Amongst the microelements, Cu and Li were detected in both extracts in similar amounts. However, BPFEE contained higher amounts of Zn, but lower amount of Fe, compared to CPFEE. The antimicrobial activity was tested against Bacillus cereus, Salmonella spp. and Candida albicans, pairs of reference strains and isolates. CPFEE resulted as a better bacteriostatic and anticandidal agent. These results are valuable in promoting further progress, development and production regarding the aromatic plant industry, pharmaceutical and food industry.

Metal coordination governs the antimicrobial efficacy of calcitermin derivatives.

Antimicrobial peptides are promising alternatives to classical antibiotics. Their microbicidal activity can arise from different mechanisms, one of which is known as nutritional immunity and has metal micronutrients and metal-binding biomolecules as its main players. Calcitermin is an antimicrobial peptide and an effective metal chelator. Its properties as an antibacterial and anti-Candida agent have been recently studied both as a free peptide and in the presence of zinc and copper ions, with which it forms stable complexes. Calcitermin derivatives have also gained attention thanks to the possibility of improving their properties, like metal-binding affinity and/or stability in biological fluids, through ad hoc modifications of the native peptide sequence. In this work, the Ala-to-Ser substitutions close to the coordination site of calcitermin have been introduced to study the impact on the biological activity and metal-binding properties. Our results show that metal coordination has a clear impact on the bioactivity of the studied compounds, to the point that the truncated fragment of calcitermin, solely containing the main metal-binding residues, also shows antimicrobial activity.

Anticandidal Effect of New Imidazole Derivatives Over Aspartic Protease Inhibition.

Candidiasis is one of the most serious microbial infections in the world. One of the main virulence factors for Candida albicans is the crucial secretion of aspartic proteases (Saps). Saps are hydrolytic enzymes that play a major role in many fungal pathophysiological processes as well as in many levels of the associations between the fungus and its host. In this work, we report on the synthesis, characterization, and anti-candida agent evaluation of a family of 13 imidazolidine-based aspartate protease inhibitors. In vitro and in silico enzyme inhibition studies have confirmed these compounds' ability to inhibit fungal aspartate protease. Based on the molecular mechanistic value scores from molecular docking and MD simulations, we selected the top compounds 5b (binding energy -13.90 kcal/mol) and 5m (binding energy -12.94 kcal/mol) from among 5a-l based on the molecular mechanistic value scores from molecular docking and MD simulations for use in in vitro validations. In the results, imidazolidine derivatives showed strong aspartic protease inhibition activity. In conclusion, compounds 5b and 5m were found as potent anti-candida agents and screened for further pre-clinical and clinical validations.

Synthesis of novel Bis-1,2,4-Triazolo[3,4-b][1,3,4]Thiadiazines from natural camphoric acid as potential anti-candidal agents

Candida species have long been attributed to various diseases like candidiasis and systemic diseases and exacerbate the symptoms of immunocompromised patients. Candida species have enzymes that could function as drug targets to decrease their pathogenicity and eradicate the fungi. This research aimed to investigate the potency of new bis-triazolothiadiazine derivatives contained in inhibiting important enzymes of C. albicans as an example, through molecular docking simulation. Thus, a novel series of bis-triazolo[3,4-b][1,3,4]thiadiazines were designed and prepared via the reaction of the most versatile, hitherto unreported 5,5′-(1,2,2-trimethylcyclopentane-1,3-diyl)bis(4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione) with the appropriate hydrazonoyl halides and phenacyl bromides. Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. The synthesized derivatives were tested against different species of Candida spp. The most effective compound was 6f followed by 6b, 6d, and 6e, where the inhibition zone ranged from 45 mm to 38 mm. By using molecular docking, which highlighted the important interactions with the amino acid residues Lys57, Leu77, Glu116, Gly114, Phe36, Thr58, and Glu32 at the point of binding, it was possible to determine the binding interactions of the produced derivatives to the fluconazole target fungi. The binding interaction energy was discovered to be −6.494 kcal/mol for the fungi candida albicans (PDB ID: 1IA2). The derivatives 6f and 6d, which demonstrated the highest efficacy, displayed significant conserved interactions with the amino acid residues at the binding site of the fluconazole fungi, in conjunction with the PDB co-crystal ligand 1IA2. The study’s results also revealed that the dG scores of the novel bis-triazolo-thiadiazines 6b-f. The study shows good docking scores with acceptable binding interactions. Finally, molecular docking studies revealed the lowest binding activity of derivatives 6e and 6c with the target fungi.

Streptomyces: a natural source of anti-Candida agents.

Introduction. There is an urgent need to source new compounds that can combat the current threat of serious infection caused by Candida spp. and contend with the problem of antimicrobial resistance. Gap. A synthesis of the evidence available from the current literature is needed to identify promising antifungal chemotherapeutics. Aim. To highlight anti-Candida compounds derived from Streptomyces spp. (a well-known source of antimicrobial compounds) that could translate to potential candidates for future clinical practice. Methodology. A comprehensive review was conducted across three scientific literature databases spanning a 13-year period. Results. We identified 151 compounds with anti-Candida activity. Amongst these, 40 were reported with very strong inhibitory activity, having minimum inhibitory concentrations (MICs) against Candida spp. of &lt;3.5 µg ml−1, 66 compounds were considered strong inhibitors and 45 compounds exhibited moderate inhibitory potential. From an analysis of the MICs, we deduced that the actinomycin-like compounds RSP01 and RSP02 were probably the most promising anti-Candida compounds. Other antifungals of note included filipin-like compounds, which demonstrated superior inhibition to amphotericin B and activity against Candida glabrata and Candida krusei, and bafilomycin derivatives, which had substantial inhibition against Candida parapsilosis. Conclusion. It is essential to recognize the limitations inherent in the quest for new antifungals, which encompass toxicity, in vivo effectiveness and constraints associated with limited data access. However, further investigation through in-depth study and emerging technologies is of paramount importance, given that there are still many more compounds to discover. This review highlights the importance of antifungal compounds derived from Streptomyces , which demonstrate robust inhibition, and, in many cases, low toxicity, making them promising candidates for the development of novel antifungal agents.

Synthesis, spectroscopic characterization studies of chelating complexes and their applications as antimicrobial agents, DNA binding, molecular docking, and electrochemical studies

N,N′‐bis(2,4‐dihydroxy benzaldehyde‐1,2‐diaminobenzene) (H4L) formed from the reaction of 2,4‐dihydroxybenzaldehyde and 1,2‐diaminobenzene was complexed with Cu (II), Co (II), Ni (II), Mn (II), and UO2(II) ions. The formed complexes have been characterized by their physical data, spectral studies such as FT‐IR, Uv–Vis., 1H &amp; 13C NMR, Mass, elemental microanalysis (C.H.N.), thermal analysis, X‐ray diffraction, and magnetic susceptibility measurements. The molecular docking between the protein receptors of the H4L ligand and its complexes was studied as theoretical method. The ligand and its metal complexes (1–5) were tested for their ability to inhibit the growth of various pathogenic microbial strains. The biological significance of the Schiff base compound and complexes as antifungal, antibacterial, and anticandidal agents as well as cytotoxicity was studied. The tested microorganisms respond better to the metal complexes than the Schiff base ligand. In comparison to the ligand, complexes, and penicillin, the UO2(II) complex (5) demonstrated the strongest antibacterial activity. In comparison to ligand, complexes, and miconazole, the UO2(II) complex (5) has antifungal activity against Aspergillus niger and Candida albicans. Complexes (1) and (5) have higher activity of antibacterial than other complexes against Pseudomonas sp. and the highest antifungal and anticandidal activity in comparison with miconazole. The ligand and its complexes showed a dose‐dependent antibacterial action according to the minimum inhibition concentration test. Using Tafel polarization and electrochemical impedance spectroscopy experiments, the protective impact of the bis‐Schiff base ligand (H4L) ligand versus Q235 Steel and its adsorption performance were investigated. The interaction between H4L Schiff base and complexes (1)–(5) and calf thymus DNA shows hypochromism effect coupled with obvious bathochromic shift.