A novel and efficient protocol for the microwave-assisted synthesis of diversely substituted 2,2\'-bisbenzimidazol-5,6\'-dicarboxylic acid (BIMCA) from the reaction of 3,4-diaminobenzoic acid with oxalic acid has been developed, which proceeds through sequential nucleophilic addition and electrophilic substitution in accordance with the Philips method. The synthetic utility of this strategy was demonstrated by the concise, one-pot synthesis of (BIMCA) and metal complexes. (BIMCA) with a [{Fe(salen)}2O] Schiff base ligand complex and new benzimidazole coordination compounds with double oxygen [(BIMCA){Fe(salen)}2] ligand complexes were obtained. The resulting [(BIMCA){Fe(salen)}2] ligand complex was then synthesized from Co(CH3COO)2.4H2O, Ni(CH3COO)2.4H2O and Cu(CH3COO)2.H2O heteronuclear complexes. The condensations proceed with good yield to give products that, in certain instances, are not readily attainable by conventional condensation techniques. The structures of the compounds were identified by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), elemental analysis and magnetic susceptibility. The mutagenic potential of the synthesized chemicals was evaluated by the Ames test towards mutant Salmonella typhimurium strains TA98 and TA100. It was recorded that these chemicals had no mutagenic action. Also, antimicrobial activities were screened by broth microdilution test. It was seen that the minimum inhibitory concentration (MIC) against Klebsiella pneumoniae, Staphylococcus aureus and Staphylococcus epidermidis was 0.195 mg/mL, followed by a MIC value of 0.390 mg/mL against Escherichia coli and Salmonella typhimurium. [(BIMCA){Fe(salen)}2Co(II)] demonstrated significant antimicrobial activity against Proteus mirabilis and Staphylococcus aureus, with an MIC of 0.195 mg/mL, followed by an MIC of 0.390 mg/mL against Pseudomonas aeruginosa, K. pneumonia and Salmonella typhimurium. The antioxidant properties were examined using various chemical assays, and [(BIMCA){Fe(salen)}2O] and (BIMCA) exhibited greater 2,2\'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging ability, when compared with other compounds. Enzyme inhibitory effects were tested against acetylcholinesterase (AChE), amylase, butyrylcholinesterase (BChE) and tyrosinase. [(BIMCA){Fe(salen)}2Cu(II)] displayed the best AChE (IC50 0.51 mg/mL), BChE (IC50 0.51 mg/mL) and tyrosinase (IC50 1.52 mg/mL) inhibitory effects. Furthermore, molecular docking calculations were performed to gain insights into the interaction between [(BIMCA){Fe(salen)}2] and AChE, and between [(BIMCA){Fe(salen)}2Cu(II)] and amylase. Both compounds showed the potential inhibition of the protein targets.

Nitroaromatic compounds (NACs) stand out as pervasive organic pollutants, prompting an imperative need to investigate their hazardous effects. Computational chemistry methods play a crucial role in this exploration, offering a safer and more time-efficient approach, mandated by various legislations. In this study, our focus lay on the development of transparent, interpretable, reproducible, and publicly available methodologies aimed at deriving quantitative structure-activity relationship models and testing them by modelling the mutagenicity of NACs against the Salmonella typhimurium TA100 strain. Descriptors were selected from Mordred and RDKit molecular descriptors, along with several quantum chemistry descriptors. For that purpose, the genetic algorithm (GA), as the most widely used method in the literature, and three alternative algorithms (Boruta, Featurewiz, and ForwardSelector) combined with the forward stepwise selection technique were used. The construction of models utilized the multiple linear regression method, with subsequent scrutiny of fitting and predictive performance, reliability, and robustness through various statistical validation criteria. The models were ranked by the Multi-Criteria Decision Making procedure. Findings have revealed that the proposed methodology for descriptor selection outperforms GA, with Featurewiz showing a slight advantage over Boruta and ForwardSelector. These constructed models can serve as valuable tools for the quick and reliable prediction of NACs mutagenicity.

Soy protein is considered to be a high-quality protein with a range of important biological functions. However, the applications of soy protein are limited due to its poor solubility and high level of allergenicity. Its peptides have been of interest because they exert the same biological functions as soy protein, but are easier to absorb, more stable and soluble, and have a lower allergenicity. Moreover, recent research found that an attachment of chemical moieties to peptides could improve their properties including their biodistribution, pharmacokinetic, and biological activities with lower toxicity. This study therefore aimed to acquire scientific evidence to support the further application and safe use of the soybean oligopeptide (OT) conjugated with allulose (OT-AL) or D-mannose (OT-Man). The anti-inflammation, cytotoxicity, and genotoxicity of OT, OT-AL, and OT-Man were investigated. The results showed that OT, AL, Man, OT-AL, and OT-Man at doses of up to 1000 µg/mL were not toxic to HepG2 (liver cancer cells), HEK293 (kidney cells), LX-2 (hepatic stellate cells), and pre- and mature-3T3-L1 (fibroblasts and adipocytes, respectively), while slightly delaying the proliferation of RAW 264.7 cells (macrophages) at high doses. In addition, the oligopeptides at up to 800 µg/mL were not toxic to isolated human peripheral blood mononuclear cells (PBMCs) and did not induce hemolysis in human red blood cells (RBCs). OT-Man (200 and 400 µg/mL), but not OT, AL, Man, and OT-AL, significantly reduced the production of NO and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells, suggesting that the mannose conjugation of soy peptide had an inhibitory effect against LPS-stimulated inflammation. In addition, the secretion of interleukin-6 (IL-6) stimulated by LPS was significantly reduced by OT-AL (200 and 400 µg/mL) and OT-Man (400 µg/mL). The tumor necrosis factor-α (TNF-α) level was significantly decreased by OT (400 µg/mL), AL (400 µg/mL), OT-AL (200 µg/mL), and OT-Man (200 and 400 µg/mL) in the LPS-stimulated cells. The conjugation of the peptides with either AL or Man is likely to be enhance the anti-inflammation ability to inhibit the secretion of cytokines. As OT-Man exhibited a high potential to inhibit LPS-induced inflammation in macrophages, its mutagenicity ability was then assessed in bacteria and Drosophila. These findings showed that OT-Man did not trigger DNA mutations and was genome-safe. This study provides possible insights into the health advantages and safe use of conjugated soybean peptides.

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BACKGROUND: Electronic cigarettes (e-cigarettes) are often advertised as a safer alternative to traditional smoking. However, recent data suggest they may not be as safe as previously believed. This study aims to evaluate the genotoxicity and mutagenicity of e-cigarette liquids.
METHODS: We randomly selected eight varieties of e-cigarette liquids from the local market in Jeddah, Saudi Arabia. We evaluated their genotoxicity using the Genotoxicity SOS-Chromo Test™ Kit. In this investigation, a rat liver S9 fraction was utilized to emulate liver metabolic function to measure any chemical substance\'s mutagenic potential. The SOS-Chromo Test was performed by recording the β-galactosidase and alkaline phosphatase activity with and without the metabolic activation enzyme (S-9).
RESULTS: All samples, except for the first two dilutions of sample 2, were nongenotoxic in the absence of the S9 activation enzyme, according to the genotoxicity analysis. However, when tested in the presence of the S9 enzyme, samples 2, 4, and 7 exhibited mutagenic activity at varying concentrations.
CONCLUSIONS: Contrary to common belief, e-cigarettes are not safe. The present investigation confirms the presence of both toxicants and carcinogens in some e-cigarette liquids. This exposure could increase users\' risk of various health complications.

The Vanilla genus is crucial for global production in food, perfume, and pharmaceutical industries. However, exploitation threatens some species, leading to extinction. Traditional communities use vanilla for medicinal purposes, and there are species like Vanilla chamissonis Klotzsch and Vanilla bahiana Hoehne with potential to occupy the market. For this, methanolic extraction of these two mentioned species was conducted alongside Vanilla planifolia. Analyzes of the cell viability, mutagenic and genotoxic potential were performed. In the Ames test, the assays were performed with concentrations from 0.5 and 5000 μg/ml and on five strains. Only Vanilla planifolia exhibited mutagenicity at the highest concentration in the TA98 strain. Viability tests were performed within a dose range of 0.05-5000 µg/ml and 24, 48, and 72-hour exposures. It was possible to observe a reduction in cell viability observed only at the highest concentration, for all three species and both cell types tested. Genotoxicity induction by the extracts was assessed at concentrations from 0.5 to 500 µg/ml through the cytokinesis-block micronucleus assay. No genotoxic damage or reduction in the Nucleus Division Index (NDI). The study found no mutagenicity, cytotoxicity, or genotoxicity in the species tested, indicating potential human use for food or pharmaceutical purposes.

N-nitrosamines and nitrosamine drug substance related impurities (NDSRIs) became a critical topic for the development and safety of small molecule medicines following the withdrawal of various pharmaceutical products from the market. To assess the mutagenic and carcinogenic potential of different N-nitrosamines lacking robust carcinogenicity data, several approaches are in use including the published carcinogenic potency categorization approach (CPCA), the Enhanced Ames Test (EAT), in vivo mutagenicity studies as well as read-across to analogue molecules with robust carcinogenicity data. We employ quantum chemical calculations as a pivotal tool providing insights into the likelihood of reactive ion formation and subsequent DNA alkylation for a selection of molecules including e.g., carcinogenic N-nitrosopiperazine (NPZ), N-nitrosopiperidine (NPIP), together with N-nitrosodimethylamine (NDMA) as well as non-carcinogenic N-nitrosomethyl-tert-butylamine (NTBA) and bis (butan-2-yl) (nitros)amine (BBNA). In addition, a series of nitroso-methylaminopyridines is compared side-by-side. We draw comparisons between calculated reaction profiles for structures representing motifs common to NDSRIs and those of confirmed carcinogenic and non-carcinogenic molecules with in vivo data from cancer bioassays. Furthermore, our approach enables insights into reactivity and relative stability of intermediate species that can be formed upon activation of several nitrosamines. Most notably, we reveal consistent differences between the free energy profiles of carcinogenic and non-carcinogenic molecules. For the former, the intermediate diazonium ions mostly react, kinetically controlled, to the more stable DNA adducts and less to the water adducts via transition-states of similar heights. Non-carcinogenic molecules yield stable carbocations as intermediates that, thermodynamically controlled, more likely form the statistically preferred water adducts. In conclusion, our data confirm that quantum chemical calculations can contribute to a weight of evidence approach for the risk assessment of nitrosamines.

Chemical compounds in the environment, which exhibit toxic and genotoxic activity, increase the mutational pressure on biota. This study aimed to investigate the genotoxic, mutagenic, and toxic effects of water from the Ile River and the Kapshagai Reservoir, both sites of active economic activities. Cytogenetic analysis of bone marrow from mice exposed to water samples from the Ile River and the Kapshagai Reservoir revealed a statistically significant increase in aberrant (p<0.05) and polyploid cells (p<0.01), as well as a decrease in the mitotic index (p<0.001), compared to the negative control. The water samples caused statistically significant increases in single- and double-strand DNA breaks in cells across various organs in the experimental mice compared to unexposed animals (p<0.001). These observations suggest the existence of chemical compounds within the water samples from the Kapshagai Reservoir and the Ile River, which exhibit genotoxic, mutagenic, and toxic properties.

Canagliflozin, Dapagliflozin, and Empagliflozin, glucagon-like peptide-1 receptor agonists, are indicated for managing type II diabetes. Although the genotoxicity profiles of these drugs are well-explored, limited information exists regarding the genotoxic potential of their impurities. In this investigation, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin underwent both in silico and in vitro assessments for mutagenic potential. Tester strains of Salmonella typhimurium and Escherichia coli were subjected to the Ames test, utilizing concentrations of up to 1 µg per plate, with and without the presence of metabolic activation. Evaluation of micronucleus induction in TK6 cells was conducted through a micronucleus test, exploring concentrations up to 500 µg/mL, with or without the presence of exogenous metabolic activation. Under the specific test conditions, the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin showed no evidence of mutagenicity or clastrogenicity, establishing their in vitro classification as nonmutagenic. These findings align with negative in silico predictions from quantitative structure-activity relationship (QSAR) analyses for mutagenicity and genotoxicity of the dimer impurities. Collectively, these studies contribute clinically relevant safety information by confirming that the dimer impurities of Canagliflozin, Dapagliflozin, and Empagliflozin are nonmutagenic and nongenotoxic, emphasizing the consistency between in silico and in vitro data.

The objective of the present study was to investigate some commonly detected halogenated textile pollutants for their bioavailability and hazardous properties. Release into artificial sweat and skin absorption in vitro were examined as well as mutagenic effects by Ames test, and skin-sensitizing properties from a peptide reactivity assay combined with a cell test. All investigated compounds were shown to migrate from the textile into sweat and be absorbed by the skin, although to a different extent. The experimental values for migration were found to be up to 390 times higher compared to literature values. Two of the studied compounds, 2,5-dinitrochlorobenzene and 3,5-dinitrobromobenzene, both exhibited mutagenic effects in the Ames test, while both 2,5-dinitrochlorobenzene and 2,6-dichlorobenzene-1,4-diamine were classified as skin sensitizers. The allergenic reactivity of the latter was found to be due to an oxidized transformation product. Risks for the induction of skin allergy and other non-carcinogenic effects from dermal exposure to the individual compounds were found low, even when considering clothing with the highest reported levels. However, the complex mixtures of chemicals often present in garments may still constitute a health risk, especially when considering the many hours of daily exposure. It is important to further study the toxicity of other frequently occurring chemicals as well as the synergistic effects of chemicals that co-occur in clothing.