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Objective: There are many causes for obesity; inappropriate dietary patterns, inadequate physical activity, and lethargic lifestyle can be mentioned as the main and most important of these causes. Due to the increasing prevalence of obesity in society, it seems necessary to study its causes and find ways to tackle this problem. Materials and Methods: This descriptive-analytical study was conducted on 380 female high school students from district 5 of Tehran, Iran, in 2012. In this research, physical activity was measured using the International Physical Activity Questionnaire (IPAQ), and dietary pattern was measured using the Food Frequency Questionnaire (FFQ). Body mass index (BMI) was also calculated. In addition, for measurement of aerobic and anaerobic powers, the 540-meter sprint and vertical jump test (Sargent Jump Test) were applied. Gathered data was analyzed using SPSS software. Results: The findings of the present study show that 24.7% of the population was overweight and obese, 67% of normal weight (natural), and 8.2% underweight (thin). Chi-square test on breakfast and classification of weight (r = -0.285 and P = 0.002) showed a negative relationship between obesity and eating breakfast. Moreover, it showed a significant positive correlation between watching television and working on the computer, and obesity. Conclusion: According to the results of this research, there is a positive and direct relationship between obesity and lack of exercise and fast food intake (P < 0.05). There is also a positive and direct relationship between physical fitness, and amount of physical activity and fruit and vegetables intake (P < 0.05). The highest rates of overweight and obesity were observed in 17 year olds.

Background: Diabetes is characterized by a lack of insulin and insensitivity to insulin. In 2013, the global diabetes population was 382 million, with 90% of them having type 2 diabetes (non-insulin-dependent). It is predicted that this number will increase to 592 million by 2035. Aim: Here, we aimed to synthesize a series of benzimidazole-based derivatives B1 - B32 with α-glucosidase inhibition potential as antidiabetic agents. Methods: Compounds B1 - B32 were prepared in three three-step reactions, and the structures were elucidated using spectroscopic methods, namely 1H NMR, 13C NMR, MS and IR. Enzyme inhibition and kinetic study were done using commercial assay kits, and molecular docking study using autodock4. Results: Bioassay data showed that twenty-four out of the thirty-two tested compounds exhibited IC50 values ranging from 44 to 745 μM, surpassing the standard molecule, acarbose (IC50: 750 μM). it was determined that the best compound, B10 , functions as a competitive inhibitor. Additionally, a molecular docking study provided insights into the interactions between the four most promising compounds ( B5 , B6 , B10 and B28 ) and the active site residues within the enzyme. Conclusion: The tested compounds are interesting α-glucosidase inhibitors, which indicates the benefit of more bioassay studies, especially in vivo studies.

α-Glucosidase inhibitory activity of galbanic acid and its new amide derivatives 3a-n were investigated. Galbanic acid and compounds 3a-n showed excellent anti-α-glucosidase activity with IC 50 values ranging from 0.3 ± 0.3 μM to 416.0 ± 0.2 μM in comparison to positive control acarbose with IC 50 value of = 750.0 ± 5.6. In the kinetic study, the most potent compound 3h demonstrated a competitive mode of inhibition with K i  = 0.57 µM. The interaction of the most potent compound 3h with the α-glucosidase was further elaborated by in vitro Circular dichroism assessment and in silico molecular docking and Molecular dynamics studies. Compound 3h was also non-cytotoxic on human normal cells. In silico study on pharmacokinetics and toxicity profile of the most potent galbanic acid derivatives demonstrated that these compounds are valuable lead compounds for further study in order to achieve new anti-diabetic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

One of the multifactorial worldwide health syndromes is diabetes mellitus which is increasing at a disturbing rate. The inhibition of α-glucosidase, an enzyme that catalyzes starch hydrolysis in the intestine, is one helpful therapeutic approach for controlling hyperglycemia related to type-2 diabetes. To discover α-glucosidase inhibitors, some 2-hydrazolyl-4-thiazolidinone hybrids ( 3a-e ) were synthesized from new one-pot reaction procedures. Next, their chemical structures were confirmed by 1 H NMR, 13 C NMR, and FT-IR spectra, and elemental analysis technique. Then, the α-glucosidase inhibitory activity of the titled compounds was evaluated. Among them, derivatives 3b and 3c revealed the highest activity against α-glucosidase compared to acarbose as a drug. Enzyme kinetic studies of the most active derivative ( 3b ) indicated a competitive inhibition. Finally, molecular modeling studies were accomplished to describe vital interactions of the most potent compounds ( 3b and 3c ) with the α-glucosidase enzyme., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Saghi Sepehri reports financial support was provided by 10.13039/501100006662Ardabil University of Medical Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC 50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC 50  = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure-activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose., (© 2024. The Author(s).)

Α-glucosidase inhibition can be useful in the management of carbohydrate-related diseases, especially type 2 diabetes mellitus. Therefore, in this study, a new series of 6-chloro-2-methoxyacridine bearing different aryl triazole derivatives were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. The most potent derivative in this group was 7h bearing para-fluorine with IC 50 values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC 50 value = 750.0 ± 10.5 μM). A kinetic study of compound 7h revealed that it is a competitive inhibitor against α-glucosidase. Molecular dynamic simulations of the most potent derivative were also executed and indicated suitable interactions with residues of the enzyme which rationalized the in vitro results., (© 2024. The Author(s).)

In this work, a novel series of N-phenylacetamide-1,2,3-triazole-indole-2-carboxamide derivatives 5a-n were designed by consideration of the potent α-glucosidase inhibitors containing indole and carboxamide-1,2,3-triazole-N-phenylacetamide moieties. These compounds were synthesized by click reaction and evaluated against yeast α-glucosidase. All the newly title compounds demonstrated superior potency when compared with acarbose as a standard inhibitor. Particularly, compound 5k possessed the best inhibitory activity against α-glucosidase with around a 28-fold improvement in the inhibition effect in comparison standard inhibitor. This compound showed a competitive type of inhibition in the kinetics. The molecular docking and dynamics demonstrated that compound 5k with a favorable binding energy well occupied the active site of α-glucosidase., (© 2024. The Author(s).)

This study describes the design, synthesis, and evaluation of a novel series of phenylthiosemicarbazide-phenoxy-1,2,3-triazole-N-phenylacetamide derivatives (7a-l) as dual inhibitors of α-glucosidase and protein tyrosine phosphatase 1-B (PTB-1B). The latter enzymes are two important targets in the treatment of type 2 diabetes. The in vitro obtained data demonstrated that all title compounds 7a-l were more potent than the standard inhibitor acarbose against α-glucosidase while only four derivatives (7a, 7g, 7h, and 7h) were more potent than the standard inhibitor suramin against PTP-1B. Furthermore, these data showed that the most potent α-glucosidase inhibitor was compound 7i, with sixfold higher inhibitory activity than acarbose, and the most potent PTP-1B inhibitor was compound 7a with 3.5-fold higher inhibitory activity than suramin. Kinetic studies of compounds 7i and 7a revealed that they inhibited their target enzymes in a competitive mode. The docking study demonstrated that compounds 7i and 7a well occupied the active site pockets of α-glucosidase and PTP-1B, respectively. In silico pharmacokinetic and toxicity assays of the most potent compounds were performed, and the obtained results were compared with those of the standard inhibitors., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

The inhibition of the α-glucosidase enzyme is crucial for targeting type 2 diabetes mellitus (DM). This study introduces a series of synthetic analogs based on thiomethylacetamide-quinoline derivatives linked to diphenyl-imidazole as highly potential α-glucosidase inhibitors. Twenty derivatives were synthesized and screened in vitro against α-glucosidase, revealing IC 50 values ranging from 0.18 ± 0.00 to 2.10 ± 0.07 μM, in comparison to the positive control, acarbose. Among these derivatives, compound 10c (IC 50  = 0.180 μM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (K i  = 0.15 μM). Docking and molecular dynamic evaluations elucidated the binding mode of 10c with the active site residues of the α-glucosidase enzyme. Moreover, in vivo assessments on a rat model of DM affirmed the anti-diabetic efficacy of 10c, evidenced by reduced fasting and overall blood glucose levels. The histopathological evaluation enhanced pancreatic islet architecture and hepatocytes in liver sections. In conclusion, novel 2-(quinoline-2-ylthio)acetamide derivatives as potent α-glucosidase inhibitors were developed. Compound 10c emerged as a promising candidate for diabetes management, warranting further investigation for potential clinical applications and mechanistic insights., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Cassia angustifolia Vahl. ( Senna ) is a medicinal plant containing anthraquinone compounds such as sennoside. Senna is primarily valued for its laxative properties. In Persian medicine, this plant has been also used to treat various disorders such as diabetes and skin hyperpigmentation. Previous studies have shown that different species of senna , such as C. articulata, C. alata, C. Siamea , C. Surattensis inhibit alpha-amylase and α-glucosidase enzymes. To the best of our knowledge, no previous evidence is available on tyrosinase and α-glucosidase inhibitory effects of the extract and different fractions of C. angustifolia leaves., Objectives: The purpose of this study was to investigate the inhibitory effect of the methanol-water extract and different fractions (hexane, chloroform, ethyl acetate, and remaining crude extract) of senna against tyrosinase and α-glucosidase and to investigate their total phenolic and sennoside B contents., Results: Our findings depicted that the methanol-water extract and fractions had no significant anti-tyrosinase activity; however, some fractions were active toward α-glucosidase. The hexane fraction and the remaining crude extract demonstrated the highest inhibition on α-glucosidase compared to acarbose (positive control). In addition, the ethyl acetate fraction contains high phenolic and hydroxy anthraquinone derivatives based on the amount of sennoside B contents equivalent to 382.25 μg/mL of gallic acid and 1.525% of sennoside B, respectively. Moreover, no correlation was observed between the phenolic and sennoside contents of different fractions and their α-glucosidase inhibitory effect., Conclusions: Considering the α-glucosidase inhibition results, the hexane fraction of C. angustifolia can be a valuable fraction for in vitro and in vivo antidiabetic studies as well as further phytochemical studies. Further studies to identify the active substances and the exact mechanism of the bioactive ingredients on the inhibitory effects of α-glucosidase can provide promising results in the future., Competing Interests: The authors declare that they have no conflicts of interests., (Copyright © 2024, Morid Ahmadi et al.)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC 50  = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC 50  = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with K i  = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

A novel, dual-faced, and hierarchical type of Janus hybrid structures (JHSs) was assembled through an in situ growing of lipase@cobalt phosphate sheets on the laccase@copper phosphate sponge-like structures. The chemical and structural information of prepared JHSs was investigated by Scanning electron microscopy-energy dispersive X-ray analysis (SEM-EDX), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction analysis (XRD). The catalytic activity, storage stability, and reusability of JHSs were then investigated. The SEM-EDX analysis clearly confirmed the asymmetric morphology of the fabricated JHSs with two distinct metal distributions. Under optimized synthesis conditions, the prepared JHSs showed 97.8 % and 100 % of laccase and lipase activity, respectively. Compared to the free biocatalysts, the immobilization resulted in ~ a 2-fold increase in laccase and lipase stability at temperatures of >40 °C. The fabricated JHSs maintained 61 % and 90 % of their original laccase and lipase activity upon 12 successive repetition cycles. Up to 80 % of Reactive Blue-19 (RB-19), an anthraquinone-based vinyl sulphone dye, was removed after 5 h treatment with the prepared JHSs (50 % higher than the free forms of laccase and lipase). The dye removal data fitted very well on the pseudo-second-order kinetic model with a rate constant of 0.8 g mg -1  h -1 . Following the bioremoval process, bacterial toxicity also decreased by about 70 %. Therefore, the prepared JHSs provide a facile and sustainable approach for the decolorization, biotransformation, and detoxification of RB-19 by integrating enzymatic oxidation and hydrolysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Somayeh Mojtabavi reports financial support was provided by Tehran University of Medical Sciences. Somayeh Mojtabavi reports a relationship with Tehran University of Medical Sciences that includes: funding grants., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ventilator-associated pneumonia (VAP) is a severe hospital-acquired infection that endangers patients' treatment in intensive care units (ICUs). One of the leading causes of VAP is biofilm formation on the endotracheal tube (ETT) during ventilation. This study reports a combination of laccase-gadolinium phosphate hybrid nanoparticles (laccase@GdPO 4 ·HNPs) and enzyme mediator with an antibiofilm property coated on the surface of the ETT. The hybrid nanostructures were fabricated through a simple, rapid, and facile laccase immobilization method, resulting in efficiency and yield percentages of 82 ± 6% and 83 ± 5%, respectively. The surface of the ETT was then functionalized and coated with the constructed HNP/catechol. The layered ETT was able to reduce the surface adhesion of Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus by 82.1%, 84.5%, and 77.1%, respectively. The prepared ETT did not affect the viability of human lung epithelial cells L929 and A549 at concentrations of 1-5 mg mL -1 . The layered ETT produced a strong computed tomography (CT) signal in comparison with iobitridol. The HNP/catechol-coated ETT exhibited a Gd 3+ release of 0.45 ppm over 72 h, indicating reduced risks of cytotoxicity arising from the metal ions. In this research we develop a biofilm-resistant and contrasting agent-based ETT coated with green synthesized laccase@GdPO 4 ·HNPs.

Diabetes mellitus is a multifactorial global health disorder that is rising at an alarming rate. One effective therapeutic approach for controlling hyperglycemia associated with type-2 diabetes is to target α-glucosidase, which catalyzes starch hydrolysis in the intestine. In an attempt to find potential α-glucosidase inhibitors, a series of twenty new quinoline linked benzothiazole hybrids (8a-t) were synthesized in good yields from suitable reaction procedures and their chemical structures were analyzed by 1 HNMR, 13 CNMR, IR, and ESI-MS analysis. The synthesized derivatives further screened for their activity against α-glucosidase. Among them, compounds 8b, 8h, 8n and 8o exhibited remarkable α-glucosidase inhibitory activity with IC 50 values ranging from 38.2 ± 0.3 to 79.9 ± 1.2 µM compared with standard drug acarbose (IC 50  = 750.0 ± 2.0 µM). Enzyme kinetic studies of the most active compound (8h) indicated a non-competitive inhibition with K i value of 38.2 µM. Moreover, the homology modeling, molecular docking and molecular dynamics simulation studies were conducted to reveal key interactions between the most active compound 8h and the targeted enzyme. These results are complementary to the experimental observations. In order to predict the druggability of the novel derivatives, the pharmacokinetic properties were also applied. These findings could be useful for the design and development of new α-glucosidase inhibitors., (© 2024. The Author(s).)

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a-o) and the structure of all derivatives was confirmed through various techniques including IR, 1 H-NMR, 13 C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC 50 values in the range of 26.0 ± 0.8-459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase., (© 2024. The Author(s).)

Because of the colossal global burden of diabetes, there is an urgent need for more effective and safer drugs. We designed and synthesized a new series of aurone derivatives possessing phenylureido or bis-phenylureido moieties as α-glucosidase and α-amylase inhibitors. Most of the synthesized phenylureidoaurones have demonstrated superior inhibition activities (IC 50 s of 9.6-339.9 μM) against α-glucosidase relative to acarbose (IC 50  = 750.0 μM) as the reference drug. Substitution of aurone analogues with two phenylureido substituents at the 5-position of the benzofuranone moiety and the 3' or 4' positions of the 2-phenyl ring resulted in compounds with almost 120-180 times more potent inhibitory activities than acarbose. The aurone analogue possessing two phenylureido substitutions at 5 and 4' positions (13) showed the highest inhibition activity with an IC 50 of 4.2 ± 0.1 μM. Kinetic studies suggested their inhibition mode to be competitive. We also investigated the binding mode of the most potent compounds using the consensually docked 4D-QSAR methodology. Furthermore, these analogues showed weak-to-moderate non-competitive inhibitory activity against α-amylase. 5-Methyl substituted aurone with 4'-phenylureido moiety (6e) demonstrated the highest inhibition activity on α-amylase with an IC 50 of 142.0 ± 1.6 μM relative to acarbose (IC 50  = 108 ± 1.2 μM). Our computational studies suggested that these analogues interact with a hydrophilic allosteric site in α-amylase, located far from the enzyme active site at the N-terminal., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Latifeh Navidpour reports financial support was provided by Tehran University of Medical Sciences., (Copyright © 2023. Published by Elsevier Inc.)

α-Glucosidase inhibition is an approved treatment for type 2 diabetes mellitus (T2DM). In an attempt to develop novel anti-α-glucosidase agents, two series of substituted imidazo[1,2-c]quinazolines, namely 6a-c and 11a-o, were synthesized using a simple, straightforward synthetic routes. These compounds were thoroughly characterized by IR, 1 H and 13 C NMR spectroscopy, as well as mass spectrometry and elemental analysis. Subsequently, the inhibitory activities of these compounds were evaluated against Saccharomyces cerevisiae α-glucosidase. In present study, acarbose was utilized as a positive control. These imidazoquinazolines exhibited excellent to great inhibitory potencies with IC 50 values ranging from 12.44 ± 0.38 μM to 308.33 ± 0.06 μM, which were several times more potent than standard drug with IC 50 value of 750.0 ± 1.5 μM. Representatively, compound 11j showed remarkable anti-α-glucosidase potency with IC 50  = 12.44 ± 0.38 μM, which was 60.3 times more potent than positive control acarbose. To explore the potential inhibition mechanism, further evaluations including kinetic analysis, circular dichroism, fluorescence spectroscopy, and thermodynamic profile were carried out for the most potent compound 11j. Moreover, molecular docking studies and in silico ADME prediction for all imidazoquinazolines 6a-c and 11a-o were performed to reveal their important binding interactions, as well as their physicochemical and drug-likeness properties, respectively., (© 2023. Springer Nature Limited.)

From the environmental point of view, azo dye industrial effluent is a major public health concern due to its toxic, carcinogenic, and teratogenic characteristics. On the other hand, using enzyme-based technologies offers a promising systematic and controllable method for removing synthetic dyes from wastewater. In the present study, yttrium (Y 3+ ) phosphate was applied for the synthesis of hybrid nanoparticles (HNPs) consisting of laccase as the green catalyst. When the association of HNPs was fixed by glutaraldehyde (GA), three-dimensional cubic structures with the regular arrangement were provided. GA increased the reusability of the fabricated hybrid nanostructures (HNSs) up to 32 successive cycles. About 85% of Direct Blue-15 was removed after a 4 h-treatment using laccase@YPO 4 •HNPs and laccase@GA@YPO 4 •HNSs. The azo dye removal data were well-fitted with a pseudo-second-order model for both types of the prepared HNSs. For the model freshwater green alga Raphidocelis subcapitata, the half maximal effective concentration (EC 50 ) of the dye decreased 10- and 100-fold after the removal with laccase@YPO 4 •HNPs and laccase@GA@YPO 4 •HNSs, respectively. GA-treated HNSs (250 U L -1 ) inhibited the biofilm formation by approximately 78%, 82%, and 79% for Escherichia coli, Staphylococcus aureus, and Bacillus subtilis, respectively. Thus, the fabricated laccase@GA@YPO 4 •HNSs could be presented as a novel, efficient, and recyclable heterogeneous biocatalyst for wastewater treatment and clean-up., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

α-Glucosidase as a carbohydrate-hydrolase enzyme is a crucial therapeutic target for type 2 diabetes. In this work, benzo[d]imidazole-amide containing 1,2,3-triazole-N-arylacetamide derivatives 8a-n were synthesized and evaluated for their inhibitory activity against α-glucosidase. In vitro α-glucosidase inhibition assay demonstrated that more than half of the title compounds with IC 50 values in the range of 49.0-668.5 μM were more potent than standard inhibitor acarbose (IC 50  = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (K i  = 40.0 µM) is a competitive inhibitor against α-glucosidase. Significantly, molecular docking and molecular dynamics studies on the most potent compound showed that this compound with a proper binding energy interacted with important amino acids of the α-glucosidase active site. Study on cytotoxicity of the most potent compounds 8c, 8e, and 8g demonstrated that these compounds did not show cytotoxic activity against the cancer and normal cell lines MCF-7 and HDF, respectively. Furthermore, the ADMET study predicted that compound 8c is likely to be orally active and non-cytotoxic., (© 2023. The Author(s).)

Non-coding RNA transcripts are RNA molecules that have mainly regulatory functions and they do not encode proteins. microRNAs (miRNAs), lncRNAs and circRNAs are major types of this family and these epigenetic factors participate in disease pathogenesis, especially cancer that their abnormal expression may lead to cancer progression. miRNAs and lncRNAs possess a linear structure, whereas circRNAs possess ring structures and high stability. Wnt/β-catenin is an important factor in cancer with oncogenic function and it can increase growth, invasion and therapy resistance in tumors. Wnt upregulation occurs upon transfer of β-catenin to nucleus. Interaction of ncRNAs with Wnt/β-catenin signaling can determine tumorigenesis. Wnt upregulation is observed in cancers and miRNAs are able to bind to 3'-UTR of Wnt to reduce its level. LncRNAs can directly/indirectly regulate Wnt and in indirect manner, lncRNAs sponge miRNAs. CircRNAs are new emerging regulators of Wnt and by its stimulation, they increase tumor progression. CircRNA/miRNA axis can affect Wnt and carcinogenesis. Overall, interaction of ncRNAs with Wnt can determine proliferation rate, migration ability and therapy response of cancers. Furthermore, ncRNA/Wnt/β-catenin axis can be utilized as biomarker in cancer and for prognostic applications in patients., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The field of nanomedicine has provided a fresh approach to cancer treatment by addressing the limitations of current therapies and offering new perspectives on enhancing patients' prognoses and chances of survival. Chitosan (CS) is isolated from chitin that has been extensively utilized for surface modification and coating of nanocarriers to improve their biocompatibility, cytotoxicity against tumor cells, and stability. HCC is a prevalent kind of liver tumor that cannot be adequately treated with surgical resection in its advanced stages. Furthermore, the development of resistance to chemotherapy and radiotherapy has caused treatment failure. The targeted delivery of drugs and genes can be mediated by nanostructures in treatment of HCC. The current review focuses on the function of CS-based nanostructures in HCC therapy and discusses the newest advances of nanoparticle-mediated treatment of HCC. Nanostructures based on CS have the capacity to escalate the pharmacokinetic profile of both natural and synthetic drugs, thus improving the effectiveness of HCC therapy. Some experiments have displayed that CS nanoparticles can be deployed to co-deliver drugs to disrupt tumorigenesis in a synergistic way. Moreover, the cationic nature of CS makes it a favorable nanocarrier for delivery of genes and plasmids. The use of CS-based nanostructures can be harnessed for phototherapy. Additionally, the incur poration of ligands including arginylglycylaspartic acid (RGD) into CS can elevate the targeted delivery of drugs to HCC cells. Interestingly, smart CS-based nanostructures, including ROS- and pH-sensitive nanoparticles, have been designed to provide cargo release at the tumor site and enhance the potential for HCC suppression., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

In this work, a new series of quinoline-quinazolinone-thioacetamide derivatives 9a-p were designed using a combination of effective pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized by simple chemical reactions and evaluated for their anti-α-glucosidase activity. Among the tested compounds, compounds 9a, 9f, 9g, 9j, 9k, and 9m demonstrated significant inhibition effects in comparison to the positive control acarbose. Particularly, compound 9g with inhibitory activity around 83-fold more than acarbose exhibited the best anti-α-glucosidase activity. Compound 9g showed a competitive type of inhibition in the kinetic study, and the molecular simulation studies demonstrated that this compound with a favorable binding energy occupied the active site of α-glucosidase. Furthermore, in silico ADMET studies of the most potent compounds 9g, 9a, and 9f were performed to predict their drug-likeness, pharmacokinetic, and toxicity properties., Competing Interests: All the authors declare that they have no conflict of interest., (This journal is © The Royal Society of Chemistry.)

In this study, a novel series of pyrano[3,2- c ]quinoline-1,2,3-triazole hybrids 8a-o were synthesized and evaluated against the α-glucosidase enzyme. All compounds showed significant in vitro inhibitory activity (IC 50 values of 1.19 ± 0.05 to 20.01 ± 0.02 μM) compared to the standard drug acarbose (IC 50 = 750.0 μM). Among them, 2-amino-4-(3-((1-benzyl-1 H -1,2,3-triazol-4-yl)methoxy)phenyl)-5-oxo-5,6-dihydro-4 H -pyrano[3,2- c ]quinoline-3-carbonitrile (compound 8k ) demonstrated the best inhibitory effect toward α-glucosidase (IC 50 = 1.19 ± 0.05 μM) with a competitive pattern of inhibition. Since compound 8k was synthesized as a racemic mixture, molecular docking and dynamics simulations were performed on R - and S -enantiomers of compound 8k . Based on the molecular docking results, both R - and S -enantiomers of compound 8k displayed significant interactions with key residues including catalytic triad (Asp214, Glu276, and Asp349) in the enzyme active site. However, an in silico study indicated that S - and R -enantiomers were inversely located in the enzyme active site. The R -enantiomer formed a more stable complex with a higher binding affinity to the active site of α-glucosidase than that of the S - enantiomer. The benzyl ring in the most stable complex (( R )-compound 8k ) was located in the bottom of the binding site and interacted with the enzyme active site, while the pyrano[3,2- c ]quinoline moiety occupied the high solvent accessible entrance of the active site. Thus, the synthesized pyrano[3,2- c ]quinoline-1,2,3-triazole hybrids seem to be promising scaffolds for the development of novel α-glucosidase inhibitors., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

An important target in the treatment of type 2 diabetes is α-glucosidase. Inhibition of this enzyme led to delay in glucose absorption and decrease in postprandial hyperglycemia. A new series of phthalimide-phenoxy-1,2,3-triazole-N-phenyl (or benzyl) acetamides 11a-n were designed based on the reported potent α-glucosidase inhibitors. These compounds were synthesized and screened for their in vitro inhibitory activity against the latter enzyme. The majority of the evaluated compounds displayed high inhibition effects (IC 50 values in the range of 45.26 ± 0.03-491.68 ± 0.11 µM) as compared to the positive control acarbose (IC 50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC 50 values of 45.26 ± 0.03 and 46.25 ± 0.89 µM. Kinetic analysis revealed that the compound 11j is a competitive inhibitor with a K i of 50.4 µM. Furthermore, the binding interactions of the most potent compounds in α-glucosidase active site were studied through molecular docking and molecular dynamics. The latter studies confirmed the obtained results through in vitro experiments. Furthermore, in silico pharmacokinetic study of the most potent compounds was also performed., (© 2023. The Author(s).)

Background: A new series of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide hybrids 11a-o was designed based on molecular hybridization of the active pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized and evaluated against α-glucosidase., Methods: The 15 various derivatives of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide scaffold were synthesized, purified, and fully characterized. These derivatives were evaluated against yeast α-glucosidase in vitro and in silico. ADMET properties of the most potent compounds were also predicted., Results: All new derivatives 11a-o (IC 50 values = 6.31 ± 0.03-49.89 ± 0.09 µM) are excellent α-glucosidase inhibitors in comparison to acarbose (IC 50 value = 750.0 ± 10.0 µM) that was used as a positive control. Representatively, (E)-2-(4-((4-((2-(1H-indole-2-carbonyl)hydrazono)methyl) phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-methoxyphenyl)acetamide 11d with IC 50  = 6.31 µM against MCF-7 cells, was 118.8-times more potent than acarbose. This compound is an uncompetitive inhibitor against α-glucosidase and showed the lowest binding energy at the active site of this enzyme in comparison to other potent compounds. Furthermore, computational calculations predicted that compound 11d can be an orally active compound., Conclusion: According to obtained data, compound 11d can be a valuable lead compound for further structural development and assessments to obtain effective and potent new α-glucosidase inhibitors., (© 2023. The Author(s).)

Background: The plants from Salvia genus contain widely distributed species which have been used in folk medicine as well as pharmaceutical and food industries., Methods: The chemical composition of 12 native Iranian Salvia species (14 plants) was identified using gas chromatography-mass spectrometry (GC-MS). Also, the inhibitory activity of all essential oils (EOs) was evaluated toward α-glucosidase and two types of cholinesterase (ChE) using spectrophotometric methods. The in vitro α-glucosidase inhibition assay was performed by the determination of p-nitrophenol (pNP) obtained from the enzymatic dissociation of p-nitrophenol-α-D-glucopyranoside (pNPG) as the substrate. In vitro ChE inhibitory assay was conducted based on the modified Ellman's procedure using the measurement of 5-thio-2-nitrobenzoic acid produced from the hydrolysis of thiocholine derivatives as the substrate, in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)., Results: Totally, 139 compounds were detected and caryophyllene oxide and trans-β-caryophyllene were the most abundant compounds in all EOs. The yield of EOs extracted from the plants were also calculated in the range of 0.06 to 0.96% w/w. Herein, α-glucosidase inhibitory activity of 8 EOs was reported for the first time and among all, S. spinosa L. was found to be the most potent inhibitor (90.5 inhibition at 500 μg/mL). Also, the ChE inhibitory activity of 8 species was reported for the first time and our results showed that the BChE inhibitory effect of all EOs was more potent than that of AChE. The ChE inhibition assay indicated that S. mirzayanii Rech.f. & Esfand. collected from Shiraz was the most potent inhibitor (72.68% and 40.6% at the concentration of 500 μg/mL, toward AChE and BChE, respectively)., Conclusions: It seems that native Salvia species of Iran could be considered in the development of anti-diabetic and anti-Alzheimer's disease supplements., (© 2023. The Author(s).)

Herein, various N'-substituted benzylidene benzohydrazide-1,2,3-triazoles were designed, synthesized, and screened for their inhibitory activity toward α-glucosidase. The structure of derivatives was confirmed using 1 H- and 13 C-NMR, FTIR, Mass spectrometry, and elemental analysis. All derivatives exhibited good inhibition with IC 50 values in the range of 0.01 to 648.90 µM, compared with acarbose as the positive control (IC 50  = 752.10 µM). Among them, compounds 7a and 7h showed significant potency with IC 50 values of 0.02 and 0.01 µM, respectively. The kinetic study revealed that they are noncompetitive inhibitors toward α-glucosidase. Also, fluorescence quenching was used to investigate the interaction of three inhibitors 7a, 7d, and 7h, with α-glucosidase. Accordingly, the binding constants, the number of binding sites, and values of thermodynamic parameters were determined for the interaction of candidate compounds toward the enzyme. Finally, the in silico cavity detection plus molecular docking was performed to find the allosteric site and key interactions between synthesized compounds and the target enzyme., (© 2023. The Author(s).)

Western lifestyle contributes to an overt increase in the prevalence of metabolic anomalies including diabetes mellitus (DM) and obesity. Prevalence of DM is rapidly growing worldwide, affecting many individuals in both developing and developed countries. DM is correlated with the onset and development of complications with diabetic nephropathy (DN), diabetic cardiomyopathy (DC) and diabetic neuropathy being the most devastating pathological events. On the other hand, Nrf2 is a regulator for redox balance in cells and accounts for activation of antioxidant enzymes. Dysregulation of Nrf2 signaling has been shown in various human diseases such as DM. This review focuses on the role Nrf2 signaling in major diabetic complications and targeting Nrf2 for treatment of this disease. These three complications share similarities including the presence of oxidative stress, inflammation and fibrosis. Onset and development of fibrosis impairs organ function, while oxidative stress and inflammation can evoke damage to cells. Activation of Nrf2 signaling significantly dampens inflammation and oxidative damage, and is beneficial in retarding interstitial fibrosis in diabetic complications. SIRT1 and AMPK are among the predominant pathways to upregulate Nrf2 expression in the amelioration of DN, DC and diabetic neuropathy. Moreover, certain therapeutic agents such as resveratrol and curcumin, among others, have been employed in promoting Nrf2 expression to upregulate HO-1 and other antioxidant enzymes in the combat of oxidative stress in the face of DM., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

New series of thioquinoline structures bearing phenylacetamide 9a-p were designed, synthesized and the structure of all derivatives was confirmed using different spectroscopic techniques including FTIR, 1 H-NMR, 13 C-NMR, ESI-MS and elemental analysis. Next, the α-glucosidase inhibitory activities of derivatives were also determined and all the synthesized compounds (IC 50  = 14.0 ± 0.6-373.85 ± 0.8 μM) were more potent than standard inhibitors acarbose (IC 50  = 752.0 ± 2.0 μM) against α-glucosidase. Structure-activity relationships (SARs) were rationalized by analyzing the substituents effects and it was shown that mostly, electron-donating groups at the R position are more favorable compared to the electron-withdrawing group. Kinetic studies of the most potent derivative, 9m, carrying 2,6-dimethylphenyl exhibited a competitive mode of inhibition with K i value of 18.0 µM. Furthermore, based on the molecular dynamic studies, compound 9m depicted noticeable interactions with the α-glucosidase active site via several H-bound, hydrophobic and hydrophilic interactions. These interactions cause interfering catalytic potential which significantly decreased the α-glucosidase activity., (© 2023. The Author(s).)

In the present study, new structural variants of 4-hydroxyquinolinone-hydrazones were designed and synthesized. The structure elucidation of the synthetic derivatives 6a-o was carried out using different spectroscopic techniques including FTIR, 1 H-NMR, 13 C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a-o exhibited good α-glucosidase inhibition with IC 50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC 50  = 752.0 ± 2.0 µM). Structure-activity relationships of this series were established which is mainly based on the position and nature of the substituent on the benzylidene ring. A kinetic study of the active compounds 6l and 6m as the most potent derivatives were also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of the enzyme were determined by molecular docking and molecular dynamic simulations., (© 2023. The Author(s).)

Colorectal cancer (CRC) is a dangerous form of cancer that affects the gastrointestinal tract. It is a major global health concern, and the aggressive behavior of tumor cells makes it difficult to treat, leading to poor survival rates for patients. One major challenge in treating CRC is the metastasis, or spread, of the cancer, which is a major cause of death. In order to improve the prognosis for patients with CRC, it is necessary to focus on ways to inhibit the cancer's ability to invade and spread. Epithelial-mesenchymal transition (EMT) is a process that is linked to the spread of cancer cells, also known as metastasis. The process transforms epithelial cells into mesenchymal ones, increasing their mobility and ability to invade other tissues. This has been shown to be a key mechanism in the progression of colorectal cancer (CRC), a particularly aggressive form of gastrointestinal cancer. The activation of EMT leads to increases in the spread of CRC cells, and during this process, levels of the protein E-cadherin decrease while levels of N-cadherin and vimentin increase. EMT also contributes to the development of resistance to chemotherapy and radiation therapy in CRC. Non-coding RNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play a role in regulating EMT in CRC, often through their ability to "sponge" microRNAs. Anti-cancer agents have been shown to suppress EMT and reduce the progression and spread of CRC cells. These findings suggest that targeting EMT or related mechanisms may be a promising approach for treating CRC patients in the clinic., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this article, different s-substituted benzimidazole-thioquinoline derivatives were designed, synthesized, and evaluated for their possible α-glucosidase inhibitory activities. The most active compound in this series, 6j (X = 4-bromobenzyl) exhibited significant potency with an IC 50 value of 28.0 ± 0.6 µM compared to acarbose as the positive control with an IC 50 value of 750.0 µM. The kinetic study showed a competitive inhibition pattern against α-glucosidase for the 6j derivative. Also, the molecular dynamic simulations were performed to determine key interactions between compounds and the targeted enzyme. The in silico pharmacodynamics and ADMET properties were executed to illustrate the druggability of the novel derivatives. In general, it can be concluded that these derivatives can serve as promising leads to the design of potential α-glucosidase inhibitors., (© 2023. The Author(s).)

In this study, new hybrids of quinazolinone-1,2,3-triazole-acetamide were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results obtained from the in vitro screening indicated that all analogs exhibited significant inhibitory activity against α-glucosidase (IC 50 values ranging from 4.8-140.2 μM) in comparison to acarbose (IC 50 = 750.0 μM). The limited structure-activity relationships suggested the variation in the inhibitory activities of the compounds affected by different substitutions on the aryl moiety. The enzyme kinetic studies of the most potent compound 9c, revealed that it inhibited α-glucosidase in a competitive mode with a K i value of 4.8 μM. In addition, molecular docking studies investigated the structural perturbation and behavior of all derivatives inside the α-glucosidase active site. Next, molecular dynamic simulations of the most potent compound 9c, were performed to study the behavior of the 9c-complex during the time. The results showed that these compounds can be considered as potential antidiabetic agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The stabilizing effect of some osmolytes including betaine, mannitol, proline, sorbitol, and trehalose (each 0.5 M) was investigated on the ultrasound-irradiated (60 kHz and 138 W, for 240 min) lipase by determination of the enzyme half-life time, evaluation of the enzymatic reaction velocity (V max ), and hydrolysis of coconut oil for production of lauric acid (the main saturated fatty acid of the oil). The enzyme conformational stability was also assessed by circular dichroism (CD) and fluorescence spectroscopy. The average half-life time of mannitol- and sorbitol-treated lipase under the ultrasound irradiation was 511 ± 3 min and 531 ± 2 min, respectively; 3-fold higher than the unirradiated enzyme. The V max value of the ultrasound-treated lipase increased from 100 ± 3 nmol min -1 in the absence of osmolyte to 500 ± 7 nmol min -1 and 500 ± 9 nmol min -1 in the presence of mannitol and sorbitol, respectively. CD and fluorescence spectra indicated that mannitol and sorbitol enhanced the rigidity of the lipase molecular conformational structure, increasing the enzyme stability against the ultrasonic field. The ultrasound-irradiated lipase was then used to hydrolyze coconut oil in the absence or presence of the selected osmolytes, which led to liberate 310 ± 6 mg g -1 , 413 ± 7 mg g -1 , and 420 ± 4 mg g -1 of lauric acid in the absence or presence of sorbitol and mannitol, respectively. In the absence of an ultrasonic field, the non-osmotically-treated lipase was able to liberate only 211 ± 5 mg g -1 of lauric acid. These promising results indicate that sorbitol and mannitol stabilize the structural conformation of lipase under an ultrasonic field which in turn could improve the enzymatic hydrolysis of coconut oil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Laccase was successfully hybridized with polyamidoamine (PAMAM) dendrimer-grafted silica-coated hercynite-copper phosphate magnetic hybrid nanoflowers (MHNFs) to increase the catalytic performance of the enzyme and apply in an effective bioremoval of gemifloxacin. For this purpose, the magnetic nanoparticles (MNPs) of hercynite were covered with a silica layer, and the core-shell SiO 2 @hercynite was then modified with PAMAM dendrimer to increase the surface area of the carrier for the enzyme attachment. Subsequently, the whole complex was hybridized with laccase and copper phosphate to attain a large surface area (104.3 m 2  g -1 ). The fabricated MHNFs acquired the entrapment yield and efficiency of 90 ± 3% and 66 ± 5%, respectively. The catalytic activity of the fabricated biocatalyst was remained up to 50% after 13 reusability cycles. Approximately 90% of gemifloxacin was removed by the constructed MHNFs after 3 h incubation by adsorption and degradation mechanisms. The biotransformation products were then identified, and degradation pathways were proposed as defluorination, decarboxylation, elimination of a cyclopropyl group, and cleavage of the pyrrolidine moiety. Furthermore, the toxicity of gemifloxacin was effectively diminished against some bacterial strains., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The development of new antidiabetes agents is necessary to obtain optimal glycemic control and overcome its complications. Different quinazolin-4(3H)-one bearing phenoxy-acetamide derivatives (7a-r) were designed and synthesized to develop α-glucosidase inhibitors. All the synthesized derivatives were evaluated against α-glucosidase in vitro and among them, compound 7b showed the highest α-glucosidase inhibition with an IC 50 of 14.4 µM, which was ∼53 times stronger than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compound 7b was a competitive type towards α-glucosidase. Also, molecular docking studies analyzed the interaction between the most potent derivative and α-glucosidase. Current findings indicate the new potential of quinazolin-4(3H)-ones that could be used for the development of novel agents against diabetes mellitus., (© 2022. The Author(s).)

Background: A series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole., Methods: The thirteen various derivatives 4a-m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed., Results: Most of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose., Conclusion: Compound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors., (© 2022. The Author(s).)

Organic-inorganic hybrid nanoflowers (HNFs) are hierarchical flower-shaped microstructures that are assembled by nanoscale petal-like nanosheets composed of both organic and inorganic constituents. Generally, inorganic parts of HNFs are transition metal phosphates and organic components are mostly enzymes and proteins; however, non-protein molecules could be also used as organic phase in some types of newly described HNFs. Recent findings indicate that they are constructed through the coordination between organic and inorganic components. HNFs are mainly used for efficient biocatalysis and highly sensitive biosensing, while they have also some other noteworthy applications such as antimicrobial agents, antigen careers, and delivery platforms for anticancer drugs. It is believed that the high surface-to-volume ratio of HNFs could tackle mass transfer limitations leading to enhance the activity of their organic constituents. The environment-friendly route of synthesis and stabilization of biomolecules upon storage are the advantages of enzyme-based HNFs. In the present review, the focuses are on designs, preparations, formation mechanisms, and remarkable applications of the conventional forms and also magnetic, multi-component, and enzyme-free HNFs. Considering the fact that HNFs are in the early stages of development, the unknown aspects and future directions of research in this field are also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

A green and efficient one-pot multi-component protocol was developed for the synthesis of some novel dihydrochromeno[4,3-b]pyrrol-3-yl derivatives through the reaction of arylglyoxals, malono derivatives, and different 4-amino coumarins in ethanol at reflux condition. In this method, all products were obtained in good to excellent yield. Next, all synthesized derivatives were evaluated for their α-glucosidase inhibitory activity. Most of the compounds displayed potent inhibitory activities with IC 50 values in the range of 48.65 ± 0.01-733.83 ± 0.10 μM compared to the standard inhibitor acarbose (IC 50  = 750.90 ± 0.14 μM). The kinetic study of compound 5e as the most potent derivative (IC 50  = 48.65 ± 0.01 μM) showed a competitive mechanism with a K i value of 42.6 µM. Moreover, docking studies revealed that dihydrochromeno[4,3-b]pyrrol-3-yl effectively interacted with important residues in the active site of α-glucosidase., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

An efficient heterogeneous natural polymer-based biocatalyst was fabricated through the immobilization of laccase onto dialdehyde inulin (DAI)-coated silica-caped magnetic nanoparticles (laccase@DAI@SiO 2 @Fe 3 O 4 ⋅MNPs). The carrier was developed using SiO 2 @Fe 3 O 4 ⋅MNPs and functionalized with DAI. The construction of immobilized laccase was confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. Immobilization yield and efficiency were calculated as 61.0 ± 0.3% and 93.0 ± 0.6%, respectively. The immobilized laccase maintained 50% and 85% of its relative activity after 25 repeated cycles and 20 days of storage at 4 °C, respectively. The prepared biocatalyst effectively eliminated ofloxacin, a fluoroquinolone-type antibiotic, with a 63% removal capacity. Besides, antimicrobial activity study on some soil microorganisms involved in the biodegradation of xenobiotics revealed that the laccase-treated ofloxacin resulted in less toxic metabolites. The obtained data indicated that the fabricated biocatalyst is promising for the removal of ofloxacin or other analogs of fluoroquinolones in the environment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3-b]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR, 1 H NMR, 13 C NMR, and elemental analysis. Inhibitory activities of the title compounds were evaluated against yeast α-glucosidase. In particular, compounds 9c, 9d, and 9h exhibited high anti-α-glucosidase activity. Representatively, compound 9c with IC 50  = 1.3 µM, was 576-times more potent than positive control acarbose. Molecular docking study of the most active compounds showed that these compounds formed important binding interactions at α-glucosidase active site. Molecular dynamics study of compound 9c was also performed and the obtained results were compared with acarbose. Compounds 9c, 9d, and 9h were also evaluated for in silico druglikeness properties and ADMET prediction. These studies showed that the title most potent compounds could be exploited as drug candidates., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a-p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1 H-NMR, 13 C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6-287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (K i value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile., (© 2022. The Author(s).)

In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC 50 values in the range of 3.2 ± 0.3-185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC 50  = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents., (© 2022. The Author(s).)

Background: Curcumin is active ingredient of turmeric The main purpose of this study is evaluating impact of curcumin on suger, hypoalgesia and inflammatory factors in diabetic mice., Materials and Methods: Male mice divided into six groups of 6. One group as a negative and the other five groups injected with Streptozotocin (STZ) (200 mg/kg). Diabetic mice in each group given different treatments for twenty-one days.After that, blood sugar and neuroathy studies have been done and tissue samples the liver were studied for gene expression., Result: Curcumin reduced blood sugar, but the rate of hypoglycemia was significantly lower than metformin group P > 0.05, and the comparison of the synergistic effect of curcumin and metformin with metformin was not significant P > 0.05. Also, in neuropathy studies, the groups which recieved curcumin and metformin have shown a significant difference with diabetic group P < 0.01, Also, by evaluating inflammatory factors, there was a significant difference in the expression of TNF-a, IL-6 and NfkB, but there is no significant difference in the expression of Sirt1 P < 0.05., Conclusions: The analgesic effect of curcumin was quite evident, probably due to the significant impact of this herbal drug in reducing the expression of inflammatory genes NF-kB, IL6, and TNF-α., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01090-4., Competing Interests: Conflict of interestThere is not any conflict of interest between authors in all steps of article preparation and project’s performance., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2022, corrected publication 2022.)

A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC 50 values in the range of 6.31 to 49.89 μM compared to standard drug acarbose (IC 50  = 750.0 ± 10.0 μM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a-o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a-o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC 50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC 50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results., (© 2022. The Author(s).)

In the present work, a new series of 14 novel phthalimide-benzenesulfonamide derivatives 4a-n were synthesized, and their inhibitory activity against yeast α-glucosidase was screened. The obtained results indicated that most of the newly synthesized compounds showed prominent inhibitory activity against α-glucosidase. Among them, 4-phenylpiperazin derivative 4m exhibited the strongest inhibition with the IC 50 value of 52.2 ± 0.1 µM. Enzyme kinetic study of compound 4m proved that its inhibition mode was competitive and K i value of this compound was calculated to be 52.7 µM. In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the target compounds over the active site of α-glucosidase. Obtained date of these studies demonstrated that our new compounds interacted as well with the α-glucosidase active site with the acceptable binding energies. Furthermore, in silico druglikeness/ADME/Toxicity studies of compound 4m were performed and predicted that this compound is druglikeness and has good ADME and toxicity profiles., (© 2022. The Author(s).)

A novel approach termed the "concentrated method" was developed for the instant fabrication of laccase@Co 3 (PO 4 ) 2 •hybrid nanoflowers (HNFs). The constructed HNFs were obtained by optimizing the concentration of cobalt chloride and phosphate buffer to reach the highest activity recovery. The incorporation of 30 mM CoCl 2 and 160 mM phosphate buffer (pH 7.4) resulted in a fast anisotropic growth of the nanomaterials. The purposed method did not involve harsh conditions and prolonged incubation of precursors, as the most reported approaches for the synthesis of HNFs. The catalytic efficiency of the immobilized and free laccase was 460 and 400 M -1 S -1 , respectively. Also, the enzymatic activity of the prepared biocatalyst was 113% of the free enzyme (0.5 U mL -1 ). The stability of the synthesized HNFs was enhanced by 400% at pH 6.5-9.5 and the elevated temperatures. The activity of laccase@Co 3 (PO 4 ) 2 •HNFs declined to 50% of the initial value after 10 reusability cycles, indicating successful immobilization of the enzyme. Structural studies revealed a 32% increase in the α-helix content after hybridization with cobalt phosphate, which improved the activity and stability of the immobilized laccase. Furthermore, the fabricated HNFs exhibited a considerable ability to remove moxifloxacin as an emerging pollutant. The antibiotic (10 mg L -1 ) was removed by 24% and 75% after 24 h through adsorption and biodegradation, respectively. This study introduces a new method for synthesizing HNFs, which could be used for the fabrication of efficient biocatalysts, biosensors, and adsorbents for industrial, biomedical, and environmental applications., (© 2022. The Author(s).)