Search Results (926)

Discovering new yeast species can be crucial for creating new types of beers. In this study, we investigated three new yeast species, Saccharomyces bayanus, Schizosaccharomyces japonicus and Schizosaccharomyces pombe var. malidevorans, which have not been previously used in the brewing industry. Colour, total acidity, bitterness, aroma profile, total phenolic, flavonoid, mineral content and organoleptic characteristics of beers fermented by these strains were analysed to discover their applicability in the brewing industry. They did not significantly affect the nutritional value and colour of the beers, but showed increased acidity compared to the control Saccharomyces cerevisiae. GC-MS (Gas Chromatography-Mass Spectrometry) analysis revealed 33 aroma compounds, some of which were identical and some unique. S. cerevisiae and S. bayanus produced a similar number (19–20) of aroma compounds, while S. japonicus produced the fewest, including some undesirable compounds. Isobutyl alcohol, isoamyl alcohol, acetol, dimethylpyrazine, acetic acid, 4-cyclopentene-1,3-dione, butyrolactone, 2-furanmethanol, phenylethyl alcohol, maltol and pyranone that provide desired aromas in beers could be found in every sample. The new yeasts significantly increased polyphenols and decreased flavonoid content. Based on the results above and the taste scores, the strains S. bayanus and S. pombe var. malidevorans may be suitable for brewing, while S. japonicus is less or only suitable for combined fermentation. Full article

A focused library of 1,2,4-thiadiazolidin-3,5-diones (THIA-1–10), previously characterized as hydrogen sulfide (H₂S) donors, was evaluated for inhibitory activity against cysteine proteases. We included two key cysteine proteases aiming at antiviral drug development—SARS-CoV-2 3CLpro (Mpro) and PLpro—alongside reference enzymes Papain and Cathepsin L. The compounds exhibited distinct selectivity profiles and inhibition mechanisms. The ability to act as covalent inhibitors of 3CLpro in the nanomolar range is of particular interest, with compounds THIA-6, -7, and -10 proving to be the most potent inhibitors of the series, and compounds THIA-1, -2, and -8 proving to be the most selective with respect to the other proteases. We explored the molecular bases of the observed activity profile of THIA-1–10 through computational studies, which supported and complemented the experimental findings, paving the way for future structure optimization. The results highlight that inhibitory potency depends not only on electrophilicity but also on the ability to access the catalytic cysteine within the active site. The dual functionality of THIA-1–10 as H₂S donors and selective cysteine protease inhibitors underscores its potential as a promising lead for therapeutic development. Full article

In this article, the 1,3-dipolar cycloaddition (1,3-DC) reactions between 4-acyl-1H-pyrrole-2,3-diones fused at the [e]-side with a heterocyclic moiety (FPDs) and diphenylnitrone are studied using Molecular Electron Density Theory (MEDT) at different computational levels. An analysis of the global reactivity descriptors has determined the role of the reagents. FPDs will act as electrophiles, while diphenylnitrone will be a nucleophile. It was found that the reactions proceed according to a one-step but asynchronous mechanism. Additionally, based on the Bonding Evolution Theory (BET) analysis of the model 1,3-DC reaction between FPDs 1b and diphenylnitrone 2, we can distinguish eight different phases. The formation of the first C1-O5 single bond takes place in phase VII through the disappearance of the V(C1) monosynaptic basin and the depopulation of the V″(O5) monosynaptic basin, while the formation of the second C2-C3 single bond begins at the last phase of the reaction through the connection of two V(C2) and V(C3) monosynaptic basins. Based on this, we can classify this reaction as a “one-step two-stage” process. Furthermore, molecular dynamics (MD) simulation analysis up to 100 ns demonstrated the stability of both the 2P3B–Ligand1 and 2P3B–Zidovudine complexes. An enhancer of shape compression was generated for ligand1, whereas Zidovudine generated a more packed and stable hydrogen bond network that would allow a better occupancy of the active site. Full article

Background: Theophylline, which is biologically important and found in tea, coffee, and cocoa beans, can be synthesized chemically or by direct extraction and concentration from natural sources. Theophylline derivatives have garnered attention in recent years for their potential therapeutic effects on Mycobacterium tuberculosis, antihistaminic, anti-inflammatory, and anticancer. Also, trifluoromethyl (CF₃) group has also been widely used in drug and agrochemical design. Methods: In this study, a series of new theophylline derivatives containing substituted trifluoromethyl and trifluoromethoxy groups were synthesized. The structures of these new compounds were confirmed by NMR, FT-IR, and elemental analyses. Additionally, the anticancer activities of the molecules were analyzed against VEGFR-2, CYP P450, and estrogen receptor by molecular docking method. Furthermore, in vitro biological effects of the compounds were comprehensively evaluated in cancer (A549 and HeLa) and normal (BEAS-2B) cells. Cell viability was assessed by MTT assay, and selectivity index (SI) values were calculated to determine tumor-specific toxicity. Results: N(7)-substituted theophyllines were prepared by the reaction of 1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theophylline) and trifluoromethyl substituted benzyl halide compounds. The synthesized N(7)-substituted theophyllines were obtained as white powder in high yield. The structure of synthesized compounds was confirmed by various spectroscopic techniques such as ¹H, ¹³C, ¹⁹F NMR, and FT-IR spectroscopy, and elemental analysis. The highest interaction was recorded as −5.69 kcal/mol for 3-CF₃ substituted against VEGFR-2 structure while the best binding affinity was determined for 4-OCF₃ substituted with −6.69 kcal/mol against Human Cytochrome P450 with in silico analysis. The in vitro anticancer activities of the molecules were also evaluated against A549 and HeLa cells, and displayed considerably higher cytotoxicity with 2-CF₃, 3-CF_3, and 4-CF₃ substituted molecules in Hela and A549 cell line. To elucidate the molecular mechanism, apoptosis-related gene expression changes were analyzed by RT-qPCR in A549 and HeLa cells treated with compound 2-CF₃. Significant upregulation of pro-apoptotic markers and downregulation of anti-apoptotic genes were observed. Consistently, ELISA-based quantification confirmed increased protein levels of Caspase-3, BAX, and Cytochrome C, and decreased BCL-2, validating the apoptotic mechanism at the protein level. Also, the antibacterial and antibiofilm activity details of the molecules were evaluated against DNA Gyrase, and SarA crystal structures by molecular docking method. The highest interaction was recorded as −5.56 kcal/mol for 2-CF₃ substituted with H-bonds with Asn46, Val71, Asp73, and Thr165 against DNA Gyrase crystal structure while 3-CF₃ substituted has the best binding affinity against SarA. The in vitro antimicrobial effects of the molecules were also evaluated. Conclusions: The synthesized molecules may provide insight into the development of potential therapeutic agents to the increasing antimicrobial resistance and biofilm-forming capacity of microorganisms. Additionally, compound 2-CF₃ substituted exhibited promising and selective anticancer activity through apoptosis induction, supported by gene and protein level evidence. Full article

To develop efficient and structurally novel anticoagulants, a library of new hybrid molecules—(Z)-1-(2-(4-arylthiazol-2-yl)hydrazineylidene)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-2-ones—was designed and synthesized through a two-step approach. The reaction of pyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide produced thiosemicarbazones, which were subsequently reacted with α-bromoacetophenones. The structure of the resulting compounds was determined by HPLC-HRMS-ESI analysis, ¹H NMR spectroscopy, and ¹³C NMR spectroscopy. X-ray diffraction analysis unambiguously confirmed the structure of the resulting substances. The synthesized compounds were tested for their anticoagulant activity in vitro. Among the tested derivatives, two substances have a dual effect and exhibit 98–100% inhibitory ability against blood coagulation factors Xa and XIa at 30 μM. IC₅₀ values were also evaluated for these compounds. The results obtained show the high potential of the synthesized derivatives in the development of new multitarget anticoagulant drugs. The docking studies confirmed the experimental results. Full article

Certain foods and specific drugs have been linked to epilepsy in the literature. Here, we query PubMed citations for the co-occurrence of epilepsy with foods and drugs, using a list of 217,776 molecules from the HMDB. Notably, the top associations with epilepsy include approved drugs and drug families, diagnostic markers, inducers, and vitamins. Drugs include fosphenytoin (40%), topiramate (37%), valproic acid (34%), hydantoin (20%), phenytoin (31%), carbamazepine (33%), carbamazepine-10,11-epoxide (40%), trimethadione (31%), gabapentin (14%), pregabalin (11%), flunarizine (7%), fenfluramine (4%), bumetanide (4%), KBr (18%), cannabidiol (14%), clonazepam (22%), nitrazepam (10%), diazepam (7%), lorazepam (6%), midazolam (3%), amobarbital (21%), phenobarbital (16%), flumazenil (7%) allopregnanolone (7%), pregnanolone (6%), epipregnanolone (6%), 3-hydroxypregnan-20-one (6%), and vitamin B6 (6%). Drug families and scaffolds include imidazolidine (18%), succinimide (10%), acetamide (7%), 2-pyrrolidinone (7%), pyrrolidine (6%), tetrahydropyridine (6%), and isoxazole (4%). Investigational compounds include cyano-7-nitroquinoxaline-2,3-dione (5%). Diagnostic markers include exametazime (10%) and quinolinic acid (3%). Inducers include flurothyl (37%), pentetrazol (32%), pilocarpine (25%), (+)-Bicuculline (8%), and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP, 6%). Our analysis highlights frequently cited associations between epilepsy and specific drugs and highlights the importance of supplementing nutrients with vitamin B6 and the ketogenic diet, which increases the gamma-aminobutyric acid (GABA)/glutamate ratio. As such, our study offers dietary approaches in the treatment of this neurodegenerative disease. Full article

The aim of this paper is to obtain ethyl (2-(methylcarbamoyl)phenyl)carbamate and its metal complexes as promising antimicrobial agents. The title compound was synthesized using the ring-opening of isatoic anhydride with methylamine and further acylation with ethyl chloroformate. All metal complexes were successfully obtained after mixing the ligand dissolved in DMSO and water solutions of the corresponding metal salts and sodium hydroxide, in a metal-to-ligand-to base ratio 1:2:2. As a result, mixed ligand complexes of ethyl 2-(methylcarbamoyl)phenyl)carbamate and 3-methylquinazoline-2,4(1H,3H)-dione were obtained. The obtained complexes were characterized by their melting points, FTIR, NMR spectroscopy, and MP-AES. Then, the antimicrobial effect of the compounds against both Gram-negative and Gram-positive bacteria, yeasts, and fungi was studied. Only the Co(II) complex showed antimicrobial activity against almost all Gram-positive and Gram-negative bacteria. The cobalt complex exhibited promising antimicrobial activity against Gram-positive Micrococcus luteus with inhibition zones of 20 mm, Listeria monocytogenes (15 mm), Staphylococcus aureus (13 mm), as well as Gram-negative Klebsiella pneumoniae (13 mm) and Proteus vulgaris (13 mm). Given the potential of metal complexes as antimicrobial agents, understanding their cytotoxic effects is crucial for evaluating their therapeutic safety. To assess the in vitro biocompatibility of the experimental compounds, a range of cell viability assays was conducted using human malignant leukemic cell lines (LAMA-84, K-562) and normal murine fibroblast cells (CCL-1). The Ni(II) complex shows IC₅₀ = 105.1 µM against human malignant leukemic cell lines LAMA-84. Based on the reported results, it may be concluded that the mixed cobalt complex of 2-(methylcarbamoyl)phenyl)carbamate and 3-methylquinazoline-2,4(1H,3H)-dione can be attributed as a promising antimicrobial agent. Future in vivo tests will contribute to establishing the antimicrobial properties of this complex. Full article

The holistic use of Moringa oleifera Lam. seeds is not as popular amongst rural South Africans. This study screened for the phytochemicals, antimicrobial, and antioxidant potentials as well identifying the compounds in the oils of South African Moringa seed oils using cost-effective thin layer chromatography bioautography and dot blot assays, because fewer studies have been conducted using seed samples from this country. The results obtained indicated that the best oil extract yield (24.04%) was obtained for hexane from 60.10 g of powdered seeds. The yield of the other extracts ranged from 6.2 to 9.5%. Positive test results were obtained for terpenoids, steroids, alkaloids, flavonoids, phenols, and tannins, with potentially good antioxidant properties for scavenging free radicals from 2,2-diphenyl-1-picrylhydrazyl (DPPH) and good antimicrobial activity against Acinetobacter baumannii (BAA 747), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 27853), and Pseudomonas aeruginosa (ATCC 27853), with the best zone of inhibition of 314.2 mm² obtained for oil extracted with hexane, followed by dichloromethane, methanol, and acetone oil extracts, respectively. The best minimum inhibitory concentration (MIC) of 0.032 mg/mL against P. aeruginosa was recorded for the hexane oil, compared with ciprofloxacin, which had an MIC of 0.0039 mg/mL against the same pathogen. The identification of the in-oil compounds proposed to mitigate inhibitory activity against the test microbes was carried out through GC-MS analysis matching our results with the GC-MS library. These compounds included ursane-3,16-diol, azetidin-2-one, 1-benzyl-4à-methyl, dibutyl phthalate, 4-methyl-2,4-bis(p-hydroxyphenyl)pent-1-ene, 1H-pyrrole-2,5-dione, 3-ethyl-4-methyl, octopamine rhodoxanthin, 29,30-dinorgammacerane-3,22-diol, 21,21-dimethy, cholan-24-oic acid, 3,7-dioxo, and benzyl alcohol. These are in addition to the stability-indicating marker compounds like oleic acid (54.9%), 9-Octadecenoic acid (z)-, methyl ester (23.3%), n-hexadecanoic acid (9.68%), among others observed over a five year period. Full article

Background: Type 2 diabetes mellitus (T2DM) presents a significant global health challenge, with obesity being a major contributing risk factor alongside genetic and non-genetic elements. Current treatments focus on reducing hyperglycemia and preventing T2DM progression, often involving drug combinations for enhanced efficacy. This study introduces two novel nitrogen-containing heterocyclic scaffolds: neocryptolepine–thiazolidinedione (NC-TZD) 8 and acridine–thiazolidinedione (AC-TZD) 11. Methods: These compounds were synthesized and characterized using various spectroscopic techniques. Their antihyperglycemic and antihyperlipidemic effects were assessed in an obesity-induced zebrafish model. Hyperglycemia was induced by immersing zebrafish in 100 mM glucose monohydrate for two weeks. Fish were then divided into groups receiving either 20 mg or 80 mg of the drugs per kg of body weight, alongside negative and positive control groups. Results: Both doses of hybrids 8 and 11 effectively restored glucose, triglyceride, insulin, and nuclear factor kappa beta (nfκβ) mRNA levels to normal. However, only the lower doses restored peroxisomal acyl-CoA oxidase (acox1) mRNA levels, with higher doses proving less effective. A molecular modeling study supported the antidiabetic potential of hybrids 8 and 11, suggesting interactions with target proteins PPAR-α and acox1. In silico ADMET analysis revealed promising oral bioavailability and drug likeness for both compounds. Conclusions: The findings indicate that both hybrids exhibit significant antihyperglycemic and antihypertriglyceridemic effects, particularly at lower doses. These results highlight the promising therapeutic potential of these novel oral bioavailable compounds in managing T2DM. Further research is warranted to elucidate their mechanisms of action. Full article

This study presents colorless polyimides (PIs) suitable for use as plastic substrates in flexible displays, designed to be compatible with controlled soft adhesion and easy delamination (temporary adhesion) processes. For this purpose, we focused on a PI system derived from norbornane-2-spiro-α-cyclopentanone-α′-spiro-2″-norbornane-5,5″,6,6″-tetracarboxylic dianhydride (CpODA) and 2,2′-bis(trifluoromethyl)benzidine (TFMB). This system was selected with the aim of exhibiting excellent optical transparency and low linear coefficient of thermal expansion (CTE) properties. However, fabricating this PI film via the conventional two-step process was challenging because of crack formation. In contrast, modified one-pot polymerization at 200 °C using a combined catalyst resulted in a homogeneous solution of PI with an exceptionally high molecular weight, yielding a flexible cast film. The solubility of PI plays a crucial role in its success. This study delves into the mechanism behind the significant catalytic effect on enhancing molecular weight. The CpODA/TFMB PI cast film simultaneously achieved very high optical transparency, an extremely high glass transition temperature (T_g = 411 °C), a significantly low linear coefficient of thermal expansion (CTE = 16.7 ppm/K), and sufficient film toughness, despite the trade-off between low CTE and high film toughness. The CpODA/TFMB system was modified by copolymerization with minor contents of another cycloaliphatic tetracarboxylic dianhydride, 5,5′-(1,4-phenylene)-exo-bis(hexahydro-4,7-methanoisobenzofuran-cis-exo-1,3-dione) (BzDAxx). This approach was effective in improving the film toughness without sacrificing the low CTE and other target properties. The peel strengths (σ_peel) of laminates comprising surface-modified glass substrates and various colorless PI films were measured to evaluate the compatibility with the temporary adhesion process. Most colorless PI films studied were found to be incompatible. Additionally, no correlation between σ_peel and PI structure was observed, making it challenging to identify the structural factors influencing σ_peel control. Surprisingly, a strong correlation was observed between σ_peel and CTE of the PI films, suggesting that the observed solid–solid lamination is closely linked to the unexpectedly high surface mobility of the PI films. The laminate using CpODA(90);BzDAxx(10)/TFMB copolymer exhibited suitable adhesion strength for the temporary adhesion process, while meeting other target properties. The modified one-pot polymerization method significantly contributed to the development of colorless PIs suitable for plastic substrates. Full article

Bioconversion of cortisone leads to the synthesis of the steroid derivatives 1,9β,17,21-tetrahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11,20-dione (SCA) and 1,9β,17,20β,21-pentahydroxy-4-methyl-19-nor-9β-pregna-1,3,5(10)-trien-11-one (SCB), which have been identified as biologically active molecules in affections associated with oxidative stress and inflammation, particularly in the skin and eye. To date, the synthesis of SCA and SCB can only be achieved through a biocatalytic approach, following a biotransformation process catalyzed by Rhodococcus rhodnii DSM 43960, a synthetic pathway that adheres to the principles of green chemistry. To further enhance the sustainability of this process, this study demonstrated that SCA and SCB can be synthesized by bioconversion in a complex medium derived from a dual upcycling process involving olive leaves (UOLM). By formulating a medium based on olive leaves, a by-product derived from the previously reported biotechnological production of lactic acid, and using a concentration of 10% v/v UOLM and 1 g/L cortisone at pH 7.5, bioconversion yields of 90 ± 4.5% were achieved, with a predominance of SCB. Investigations into the addition of supplements, such as tryptone, peptone, and corn steep liquor (CSL), to assess potential improvements in yield were conducted, but no significant positive variations were observed. For the first time, bioactive steroids were synthesized from a medium obtained through a dual upcycling process of olive leaves, introducing an innovative method that opens new possibilities for the investigation of a second generation of biosteroids synthesized from lignocellulosic feedstocks. Full article

Fused 1,2,5-chalcogenadiazoles are often used as biologically active compounds and organic optovoltaic materials. [1,2,5]Thiadiazolo[3,4-b]pyrazines are much less studied due to difficulties in their preparation. In this communication, [1,2,5]thiadiazolo[3,4-b]pyrazine-5,6(4H,7H)-dione, a key precursor for the synthesis of 5,6-dihalo-[1,2,5]thiadiazolo[3,4-b]pyrazines, was prepared via condensation of 1,2,5-thiadiazole-3,4-diamine with oxalic acid or oxalyl chloride. The structure of the newly synthesized compound was established by elemental analysis, high-resolution mass spectrometry, ¹H and ¹³C NMR, IR spectroscopy, and mass spectrometry. Full article

Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute a useful alternative for the treatment of these patients. We focused on the use of lurasidone in children and adolescents with bipolar disorder. Methods: On 11 June 2025, we used the following strategy on PubMed: lurasidone AND (“bipolar disorder” OR “bipolar depression” OR mania OR manic). We filtered for humans and ages 0–18 years and included case reports and clinical studies. Similar strategies adapted to each database were used to carry out our systematic review on CINAHL, PsycINFO/PsycARTICLES, Scopus, and the ClinicalTrials.gov register on the same date. We excluded reports without children/adolescent participants, those grouping adult participants with children/adolescents without providing data separately, reviews, and opinions/editorials with no data. Eligibility was determined through Delphi rounds; it was required that consensus was reached among all authors. We followed the PRISMA-2020 Statement. Results: Our search produced 38 results on PubMed on 11 June 2025. We included four case reports/series and five studies. One additional eligible study emerged from our Scopus inquiry, raising the number of eligible studies to six. One case series was moderately positive; one case report was neutral, another was positive, and one reported the induction of mania. The six longitudinal studies involved 16,735 participants and showed generally good efficacy. Conclusions: The use of lurasidone in adolescents/children with bipolar disorder obtains favorable results regarding the excitatory and depressive symptoms of bipolar disorder with no significant side effects. Full article

The study investigated the antinociceptive effects of four compounds (F1–F4) based on a 1H-isoindole-1,3(2H)-dione core, using various in vivo pain models—tonic (formalin test), neurogenic (capsaicin and glutamate tests), neuropathic (oxaliplatin-induced model of peripheral neuropathy as well as the streptozotocin-induced model of painful diabetic neuropathy), and inflammatory (carrageenan-induced). Pharmacokinetic parameters were also assessed. In the capsaicin test, F1, F2, and F4 (5–20 mg/kg) significantly reduced pain, while compound F3 was only active at 20 mg/kg. In the glutamate test, F1, F2, and F3 (5–20 mg/kg) demonstrated the most pronounced effect. In phase I of the formalin test, compounds F1 and F2 were active at doses of 5 and 10 mg/kg, respectively, while F3 and F4 exhibited activity only at the 20 mg/kg dose. In phase II, a dose-dependent reduction in pain was observed, with the weakest effect noted at F4. At a dose of 20 mg/kg, the compounds significantly reduced edema and carrageenan-induced pain, but to a lesser extent than ketoprofen. The compounds tested (10 mg/kg) showed significant anti-allodynic activity in the oxaliplatin- and streptozotocin-induced neuropathy pain models. All compounds demonstrated favorable pharmacokinetic results. The results of this study indicate that the compounds have a broad analgesic spectrum of activity. Full article

This study introduces a newly synthesized Co(II) phthalocyanine complex (Co-Pc, 4) incorporating two (mercapto-terphenyl)thio-dione substituents, along with a detailed exploration of its structural, spectroscopic, and binding characteristics. The key precursor, 4-[(4′′-mercapto-[1,1′:4′,1′′-terphenyl]-4-yl)thio]phthalonitrile (compound 3), was first obtained and subsequently used to construct the phthalocyanine macrocycle through cyclotetramerization in the presence of cobalt and zinc salts under heat and vacuum in dimethylformamide. The resulting compounds (3 and 4) were characterized using a comprehensive array of analytical techniques, including elemental analysis, UV–Vis spectroscopy, FT-IR, ¹H-NMR, and Q-TOF mass spectrometry. Additionally, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were employed to elucidate the electronic structure and geometrical features of Co-Pc 4, providing theoretical support for the experimental findings. The integration of theoretical and experimental findings provides in-depth insight into the electronic behavior and reactivity of compound 4, highlighting its promise as a candidate for photovoltaic applications. Further studies may investigate how structural modifications influence these properties, potentially leading to improved device performance. Full article