Search Results (31)

Food deterioration is largely driven by microbial activity, particularly by fungi producing mycotoxins exhibiting mutagenic and carcinogenic effects. Garlic (Allium sativum L.), valued for its antimicrobial and anti-inflammatory properties, is widely recognized as a natural food preservative; however, the high moisture content and intense respiration of freshly harvested garlic accelerate enzymatic degradation of its bioactive compounds, making post-harvest processing essential to preserve its functional properties. This study evaluated the preservative potential of convectively dried garlic (50–90 °C) by testing the antifungal activity of its extracts (6.3–0.8%) against Aspergillus parasiticus, while a modeling approach was employed to quantitatively describe this phenomenon. The antioxidant activity and rehydration capacity were also analyzed. The results demonstrated that both drying temperature and extract concentration significantly influenced fungal growth kinetics. The strongest inhibition was observed for extracts from raw garlic and garlic dried at 50 °C, whereas extracts from samples dried at 70–90 °C only partially suppressed the microbial activity. Predictive modeling accurately described fungal growth (MAE = 1.9, R² = 0.995), enabling its application in optimizing food preservation strategies. Antioxidant activity was highest in raw garlic, decreased significantly in garlic dried at 50 °C, and then increased progressively with rising drying temperature. The study highlights the need to maintain a balance in drying conditions that ensures efficient drying kinetics while preserving bioactive, functional, and antifungal properties. Full article

Azo dyes demonstrate dose-dependent carcinogenic and mutagenic effects in exposed cells. Among remediation approaches, microbial adsorption is the most sustainable and environmentally friendly method for eliminating azo dyes. A novel Aspergillus terreus silica composite was developed as a sustainable adsorbent for crystal violet dye (CVD) removal. The fungal strain was isolated from dye wastewater and was genetically identified by 18S rRNA gene sequencing. Dried mycelia of A. terreus (PX920301) were combined with SiO₂ (1:1 w/w) through iterative hydration-drying cycles, yielding a composite characterized by FTIR analyses. Removal CVD %, adsorption capacity, and CVD residual were calculated, and the adsorption process was optimized using Box–Behnken design (four factors, 25 runs). The biosafety of the composite was assessed for phytotoxicity and microbial toxicity. The composite was also applied to real dyes wastewater collected from the bacteriological laboratory. Aspergillus terreus-silica composite showed the highest CVD removal percentage by 85.4%, adsorption capacity (qe) 121.1 mg/L, and lowest CVD residual by 7.26 mg/L, followed by the dried active mycelia (DA-mycelia) with CVD removal 40.23%, adsorption capacity (qe) 57.05 mg/L, and CVD residual by 29.73 mg/L. Optimization data cleared that the maximum experimental values of CVD removal (%) was 99.59% (predicted value 100%) obtained in run number (4) using initial CVD concentration (200 mg/L), pH (8), adsorbent composite weight (0.1 g), and contact time (48 h). Biosafety evaluation demonstrated negligible phytotoxicity against Triticum aestivum seedlings post-treatment, with restored germination and growth comparable to controls. Microbial toxicity assays via well-diffusion to seven microbial isolates confirmed no toxic activities against the tested bacteria, yeast, and fungi, underscoring the composite’s environmental safety. The composite could decolorize the real dye wastewater of laboratories by 95.37%. In conclusion, A. terreus mycelial-silica composite offers a cost-effective, sustainable, and eco-friendly alternative solution for dye bioremediation. Full article

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents. Full article

The increasing demand for advanced cosmetic formulations based on natural biopolymers has stimulated the design of multifunctional and sustainable skin care products. Hyaluronic acid (HA) and silk proteins are widely recognized for their hydrating, barrier-supportive, and biocompatible properties. This study aimed to develop a novel topical formulation, integrating low- and medium molecular weight hyaluronic acid (LMW-HA and MMW-HA), encapsulated sodium hyaluronate (NaHA), silk, and hydrolyzed silk as active components, aiming to enhance skin barrier function and biocompatibility. The formulation was subjected to comprehensive physicochemical characterization including evaluation of appearance, odor, color, pH, viscosity, and stability, all assessed over 30 days and microbiological stability testing under controlled storage conditions. Safety evaluation followed a dual-phase strategy: (i) in silico toxicological screening of individual ingredients, including sensitization, and mutagenicity predictions, and (ii) in vivo skin compatibility assessment in 25 human volunteers using a semi-occlusive patch test. The formulation demonstrated good physicochemical stability, as pH remained stable, and viscosity showed no significant changes, confirming structural integrity, indicating preserved structural and microbiological stability throughout the study period. The in silico assessment indicated no mutagenic and/or sensitizing alerts and favorable safety margins for all components, confirming the safety profile of each ingredient, supporting their suitability for dermocosmetic use, while in vivo evaluation revealed no significant adverse effects, with irritation scores indicating no skin reaction (erythema or edema) across the test population. These findings support the potential of this novel biopolymer-based formulation as a safe and well-tolerated dermocosmetic product, aligning with principles of sustainable development and biomimetic design. Full article

Background: The Ames test, a biological assay employing various strains of Salmonella typhimurium, serves as a cornerstone in genetic toxicology for evaluating the mutagenic and potentially carcinogenic properties of chemical compounds. However, experimental testing is resource-intensive and time-consuming for screening the vast chemical space of existing and novel drug candidates in pharmaceutical development. Methods: To address this limitation, we have developed the Ames Mutagenicity Predictor web application, which predicts mutagenic activity in the Ames test for given structural formulas across a comprehensive panel of different bacterial strains. The application utilizes advanced structure–activity relationship (SAR) models generated by PASS (Prediction of Activity Spectra for Substances) v2024 software. The training set comprised 3250 compounds with experimentally determined mutagenicity across 69 different strains, compiled from peer-reviewed literature and established databases, and 4285 non-mutagenic compounds from the WWAD as negative examples. Results: Leave-one-out cross-validation (LOOCV) of the 69 strain-specific models yielded an average Invariant Accuracy of Prediction (IAP) of about 0.944, and for the unspecified mutagenicity, a value of 0.962 was obtained. Conclusions: These validated models have been integrated into a freely accessible web application Ames Mutagenicity Predictor that enables users to input compound structures through multiple formats: a built-in chemical editor, SMILES notation, or compound name search. The application generates comprehensive reports detailing the predicted probability of positive Ames test results for each individual strain, providing researchers with detailed mutagenicity profiles. Full article

(1) Background: Low-molecular-weight hyaluronic acid displays moisturizing and anti-aging properties and reduces UV-induced inflammation when applied topically. A 3 kDa sodium hyaluronate oligosaccharide (Extra-Low HA) was designed, and studies were performed to evaluate its safety for cosmetic applications. (2) Methods: The ability of the Extra-Low HA (ExLMW-HA) to penetrate skin was evaluated. Then, pro-inflammatory cytokines were quantified in the culture medium of skin explants following ExLMW-HA application with or without inflammation inducer (PMA). Finally, four predictive in vitro tests (Keratinosens^™, kDPRA, Ames’ test, micronucleus test) were conducted to assess the safety of ExLMW-HA. (3) Results: The molecule permeates skin down to the living epidermis and possibly interacts with the dermal compartment. The oligosaccharide did not induce TNF-α, IL-1β, IL-1α, CXCL2, CCL3, or IL-15, neither in basal nor in stressed conditions. ExLMW-HA is not predicted to be a skin sensitizer or a mutagenic or genotoxic substance. (4) Conclusions: This 3 kDA HA is considered safe for use in topical application at the tested dosage. Full article

Toxicological risk assessment of chemicals without experimental toxicity data often relies on in silico predictions. However, models designed to predict inhalation toxicity associated with exposure to volatile chemicals in solution are unavailable. The aim of this research was to develop an approach to estimate toxicology-based maximum solution concentrations for novel odorants using in silico structure-based predictions. The decision trees were adapted from established open-source models for assessing mutagenicity (rule-based, ISS in vitro mutagenicity decision tree) and systemic toxicity (revised Cramer decision tree). These were implemented using Toxtree (v3.1.0), a freely available program. Thresholds of toxicologic concern (TTC) were then assigned based on the predicted hazard classification. We then used predicted vapor pressure derived from MPBPWIN™ using US EPA EPI Suite to calculate a solution concentration where inhalation exposure to a defined headspace volume would not exceed the TTC. The approach was evaluated using a published dataset of 143 chemicals with repeat exposure inhalation toxicity data, yielding health-protective predictions for 98.6% of the test set. This demonstrates that the proposed in silico approach enables the estimation of safe toxicology-based maximum solution concentrations for chemicals using open-source models and software. Full article

Background: Derivatives of Pyrido[2,3-d]pyrimidine-6-carboxylate are promising multi-target scaffolds. This study focused on synthesizing 16 amino-functionalized derivatives and evaluating their dual anticancer and antibacterial activities, supported by mechanistic and computational analyses. Objectives: Design and synthesize derivatives, evaluate cytotoxicity against HeLa, HepG-2, and MCF-7 (selectivity against WI-38), investigate EGFR^WT and EGFR^T790M inhibition, assess cell cycle, apoptosis, and migration effects, antibacterial efficacy against E. coli and P. aeruginosa, and perform in silico ADMET, docking, molecular dynamics, DFT, and antiviral predictions. Methods: Synthesized 16 derivatives; tested for cytotoxicity, EGFR inhibition, cell cycle, apoptosis, migration; assessed antibacterial activity; performed ADMET profiling, molecular docking, molecular dynamics, and DFT calculations. Results: Derivatives 1, 2, and 7 showed highest cytotoxicity (IC₅₀ = 3.98–17.52 μM; WI-38 IC₅₀ = 64.07–81.65 μM). Compound 1 potently inhibited EGFRWT (IC₅₀ = 0.093 μM) and EGFRT790M (IC₅₀ = 0.174 μM), induced G0/G1 arrest (74.86%) and apoptosis (26.37%), and reduced MCF-7 migration (69.63%). Moderate antibacterial activity observed (MIC = 50 μg/mL). ADMET indicated favorable pharmacokinetics, low CYP inhibition, negative mutagenicity, and oral toxicity class III. Molecular dynamics confirmed stable binding (EGFRWT RMSD 3 Å; EGFRT790M 3.5–4.6 Å) with persistent hydrogen bonds. In silico antiviral evaluation suggested strong binding to HCV NS5A (–9.36 kcal/mol), SARS-CoV-2 Mpro (–9.82 kcal/mol), and E.coli DNA gyrase (–10.25 kcal/mol). Conclusions: Compound 1 exhibits dual anticancer and antibacterial activity, supported by mechanistic and computational analyses, highlighting pyrido[2,3-d]pyrimidines as promising multi-target therapeutic scaffolds. Full article

A novel skin test for an in vivo assessment of SARS-CoV-2-specific T-cell immunity was developed using CoronaDermPS, a multiepitope recombinant polypeptide encompassing MHC II–binding CD4+ T-cell epitopes of the SARS-CoV-2 structural proteins (S, E, M) and full length nucleocapsid (N). In silico epitope prediction and modeling guided antigen design, which was expressed in Escherichia coli, was purified (>95% purity) and formulated for intradermal administration. Preclinical evaluation in guinea pigs, mice, and rhesus macaques demonstrated a robust delayed type hypersensitivity (DTH) response at optimal doses (10–75 µg), with no acute or chronic toxicity, mutagenicity, or adverse effects on reproductive organs. An integrated clinical analysis included 374 volunteers stratified by vaccination status (EpiVacCorona, Gam-COVID-Vac, CoviVac) prior to COVID-19 infection (Wuhan/Alpha, Delta, Omicron variants), and SARS-CoV-2–naïve controls. Safety assessments across phase I–II trials recorded 477 adverse events, of which >88% were mild and self-limiting; no severe or anaphylactic reactions occurred. DTH responses were measured at 24 h, 72 h, and 144 h post-injection by papule and hyperemia measurements. Overall, 282/374 participants (75.4%) exhibited a positive skin test. Receiver operating characteristic analysis yielded an overall AUC of 0.825 (95% CI: 0.726–0.924), sensitivity 79.5% (95% CI: 75.1–83.3%), and specificity 85.5% (95% CI: 81.8–88.7%), with comparable diagnostic accuracy across vaccine, and variant subgroups (AUC range 0.782–0.870). CoronaDerm-PS–based skin testing offers a simple, reproducible, and low-cost method for qualitative evaluation of T-cell–mediated immunity to SARS-CoV-2, independent of specialized laboratory equipment (Eurasian Patent No. 047119). Its high safety profile and consistent performance across diverse cohorts support its utility for mass screening and monitoring of cellular immune protection following infection or vaccination. Full article

This study aimed to assess the chemical composition and antibacterial potential of essential oils (EOs) from two plants: clove buds (Syzygium aromaticum) and fennel seeds (Foeniculum vulgare) EOs. The major compounds, eugenol and estragole, were isolated from these oils and tested against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. The EOs were obtained via hydrodistillation and analyzed using Gas Chromatography–Mass Spectrometry (GC-MS). Clove oil was found to be rich in eugenol (68.51%), while fennel seed oil was dominated by estragole (93.30%). Antibacterial activity, assessed by the agar disc diffusion method and supported by MIC/MBC testing, revealed that eugenol exhibited the highest efficacy, with MIC values ranging from 0.58 to 1.15 mg/mL and MBC values from 1.15 to 2.30 mg/mL, particularly against S. aureus and P. aeruginosa. In silico analysis was conducted to evaluate pharmacokinetics, toxicity, and molecular docking interactions. ADME predictions indicated good oral bioavailability and high membrane permeability for both compounds, with eugenol displaying superior solubility and better compliance with Lipinski’s Rule of Five. Molecular docking simulations confirmed the antibacterial potential, with eugenol showing stronger binding affinities to bacterial targets (−7.8 kcal/mol), forming more stable and diverse interactions compared to estragole. However, toxicity predictions indicated potential mutagenic, carcinogenic, and cardiotoxic (hERG inhibition) risks for both compounds. Full article

Background/Objectives: This research reports the synthesis and evaluation of novel charged thienobenzo-triazoles as non-selective cholinesterase inhibitors (AChEs and BChEs), their anti-inflammatory properties, and a computational study. Methods: Fifteen derivatives were created through photochemical cyclization and quaternization of the triazole core. The compounds were tested for AChE and BChE inhibition. They showed greater potency and selectivity toward BChE. Results: The most potent compound, derivative 14, inhibited BChE with an IC₅₀ of 98 nM, while derivative 9 also displayed significant anti-inflammatory activity by inhibiting LPS-induced TNF-α production (IC₅₀ = 0.66 µM). Molecular docking revealed that triazolinium salts form key π-π and electrostatic interactions within enzyme active sites. In silico predictions indicated favorable ADME-Tox properties for compounds 9 and 11, including low mutagenicity and moderate CNS permeability. Conclusions: These findings highlight the potential of new charged triazolinium salts as peripherally selective cholinesterase inhibitors with additional anti-inflammatory potential. Full article

In the environment, the class of chemicals known as polycyclic aromatic hydrocarbons (PAHs) behave somewhat differently. This review covers situations where PAHs can be ‘labile’ and where they can be persistent. The in-silico prediction of toxicity and the properties of selected 29 PAHs were estimated using programs developed by the U.S. Environmental Protection Agency (EPA), such as the Estimation Programs Interface (E.P.I.) and the Toxicity Estimation Software Tool (version 5.1.2) (TEST), with online software such as SwissADME and SwissDock. TEST was used to estimate the LC₅₀ of the fathead minnow (with a range of 14.53 mg/L for 1-indanone and 2.14 × 10⁻² mg/L for cyclopenta[c,d]pyrene), the LC₅₀ of Daphnia magna (with a range of 14.95 mg/L for 1-indanone and 7.53 × 10⁻² mg/L for coronene), the IGC₅₀ of Tetrahymena pyriformis (with a range of 66.14 mg/L for 1-indanone and 0.36 mg/L for coronene), the bioconcentration factor (8.36 for 1,2-acenaphthylenedione and 910.1 for coronene), the developmental toxicity (0.30 (−) for 1,2-acenaphthylenedione and 0.82 (+) for 4-hydroxy-9-fluorenone), and the mutagenicity (0.25 (−) for 2-methyl-9-fluorenone and 1.09 (+) for coronene). The carbon chain and molecular weight have a significant effect on the properties of PAHs. Overall, it was found that PAHs with a lower molecular weight (LMW) have a higher water solubility and LC₅₀ value and a smaller LogKow value, whereas the opposite is true for heavier PAHs, with TEST predicting that PAHs with an MW of over 168.2 g/mol, with a few exceptions, are mutagenic. Hence, LMW PAHs have a higher potential to be in the environment but are less toxic. Full article

The present investigation reports the efficient multistep synthesis of 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) in good yields. All the 1-(1,3-dioxoisoindolin-2-yl)-3-aryl urea analogs (7a–f) were characterized by spectroscopic techniques. Five among the six compounds were tested against 56 cancer cell lines at 10 µM as per the standard protocol. 1-(4-Bromophenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7c) exhibited moderate but significant anticancer activity against EKVX, CAKI-1, UACC-62, MCF7, LOX IMVI, and ACHN with percentage growth inhibitions (PGIs) of 75.46, 78.52, 80.81, 83.48, 84.52, and 89.61, respectively. Compound 7c was found to exhibit better anticancer activity than thalidomide against non-small cell lung, CNS, melanoma, renal, prostate, and breast cancer cell lines. It was also found to exhibit superior anticancer activity against melanoma cancer compared to imatinib. Among the tested compounds, the 4-bromosubstitution (7c) on the phenyl ring demonstrated good anticancer activity. Docking scores ranging from −6.363 to −7.565 kcal/mol were observed in the docking studies against the molecular target EGFR. The ligand 7c displayed an efficient binding against the EGFR with a docking score of −7.558 kcal/mol and displayed an H-bond interaction with Lys745 and the carbonyl functional group. Compound 7c demonstrated a moderate inhibition of EGFR with an IC₅₀ of 42.91 ± 0.80 nM, in comparison to erlotinib (IC₅₀ = 26.85 ± 0.72 nM), the standard drug. The antioxidant potential was also calculated for the compounds (7a–f), which exhibited good to low activity. 1-(2-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7f) and 1-(4-Methoxyphenyl)-3-(1,3-dioxoisoindolin-2-yl)urea (7d) demonstrated significant antioxidant activity with IC₅₀ values of 15.99 ± 0.10 and 16.05 ± 0.15 µM, respectively. The 2- and 4-methoxysubstitutions on the N-phenyl ring showed good antioxidant activity among the series of compounds (7a–f). An in silico ADMET prediction studies showed the compounds’ adherence to Lipinski’s rule of five: they were free from toxicities, including mutagenicity, cytotoxicity, and immunotoxicity, but not for hepatotoxicity. The toxicity prediction demonstrated LD₅₀ values between 1000 and 5000 mg/Kg, putting the compounds either in class IV or class V toxicity classes. Our findings might create opportunities for more advancements in cancer therapeutics. Full article

Alternariol is a metabolite produced by Alternaria fungus that can contaminate a variety of food and feed materials. The objective of the present paper was to provide a prediction of Phase I and II metabolites of alternariol and a detailed ADME/Tox profile for alternariol and its metabolites using an in silico working model based on the MetaTox, SwissADME, pKCMS, and PASS online computational programs. A number of 12 metabolites were identified as corresponding to the metabolomic profile of alternariol. ADME profile for AOH and predicted metabolites indicated a moderate or high intestinal absorption probability but a low probability to penetrate the blood–brain barrier. In addition to cytotoxic, mutagenic, carcinogenic, and endocrine disruptor effects, the computational model has predicted other toxicological endpoints for the analyzed compounds, such as vascular toxicity, haemato-toxicity, diarrhea, and nephrotoxicity. AOH and its metabolites have been predicted to act as a substrate for different isoforms of phase I and II drug-metabolizing enzymes and to interact with the response to oxidative stress. In conclusion, in silico methods can represent a viable alternative to in vitro and in vivo tests for the prediction of mycotoxins metabolism and toxicity. Full article

Chagas disease (CD) caused by the protozoan Trypanosoma cruzi affects more than six million people worldwide. Treatment is restricted to benznidazole (Bz) and nifurtimox (Nf) that display low activity in the later chronic stage besides triggering toxic events that result in treatment abandonment. Therefore, new therapeutic options are necessary. In this scenario, natural products emerge as promising alternatives to treat CD. In the family Plumbaginaceae, Plumbago sp. exhibits a broad spectrum of biological and pharmacological activities. Thus, our main objective was to evaluate, in vitro and in silico, the biological effect of crude extracts of root and of aerial parts of P. auriculata, as well as its naphthoquinone Plumbagin (Pb) against T. cruzi. The phenotypic assays revealed potent activity of the root extract against different forms (trypomastigote and intracellular forms) and strains (Y and Tulahuen), with a compound concentration that reduced 50% of the number of the parasite (EC₅₀) values ranging from 1.9 to 3.9 µg/mL. In silico analysis showed that Pb is predicted to have good oral absorption and permeability in Caco2 cells, besides excellent probability of absorption by human intestinal cells, without toxic or mutagenic potential effects, not being predicted as a substrate or inhibitor of P-glycoprotein. Pb was as potent as Bz against intracellular forms and displayed a superior trypanosomicidal effect (about 10-fold) in bloodstream forms (EC₅₀ = 0.8 µM) as compared to the reference drug (8.5 µM). The cellular targets of Pb on T. cruzi were evaluated using electron microscopy assays and the findings on bloodstream trypomastigotes showed several cellular insults related to the autophagic process. Regarding toxicity in mammalian cells, the root extracts and the naphthoquinone present a moderate toxic profile on fibroblasts and cardiac cell lines. Then, aiming to reduce host toxicity, the root extract and Pb were tested in combination with Bz, and the data showed additive profiles with the sum of the fractional inhibitory concentration indexes (ΣFICIs) being 1.45 and 0.87, respectively. Thus, our work reveals the promising antiparasitic activity of Plumbago auriculata crude extracts and its purified naphthoquinone Plumbagin against different forms and strains of Trypanosoma cruzi in vitro. Full article