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Abstract 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.

Abstract 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, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 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.

Abstract 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 IC50 values in the range of 49.0–668.5 μM were more potent than standard inhibitor acarbose (IC50 = 750.0 µM). The most promising inhibitor was N-2-methylphenylacetamid derivative 8c. Kinetic study revealed that compound 8c (Ki = 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.

Abstract 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 (IC50 values in the range of 45.26 ± 0.03–491.68 ± 0.11 µM) as compared to the positive control acarbose (IC50 value = 750.1 ± 0.23 µM). Among this series, compounds 11j and 11i represented the most potent α-glucosidase inhibitory activities with IC50 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 Ki 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.

Abstract 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, 1H-NMR, 13C-NMR, and elemental analysis, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 6a–o exhibited good α-glucosidase inhibition with IC50 values ranging between 93.5 ± 0.6 to 575.6 ± 0.4 µM as compared to the standard acarbose (IC50 = 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.

In the present study, novel series of kojic acid derivatives conjugated to amino pyridine moiety were designed and synthesized to explore their inhibitory activity against tyrosinase. To this end, the structure of all derivatives was characterized by 1H NMR, 13C NMR, FT-IR, and elemental analysis. Next, all derivatives were evaluated against tyrosinase compared to the kojic acid as positive control and exhibited different inhibitory potencies. Furthermore, the antioxidant potential of all derivatives was determined. The kinetic analysis of the most active agent revealed that 3-hydroxy-6-(hydroxymethyl)-2-((3-nitrophenyl)(pyridin-2-ylamino)methyl)-4H-pyran-4-one (4h) binds to the enzyme in the uncompetitive mode of action. The docking analysis and molecular dynamic simulations showed considerable binding affinity and significant interactions with tyrosinase enzyme to target the melanogenesis pathway, proposing them as potent candidates to control hyperpigmentation in the future.

Abstract Background Angiotensin receptor blocker and a neprilysin inhibitor (ARNI) has emerged as an innovative therapy for patients of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to assess the safety and tolerability of Sacubitril/Valsartan in patient with HFrEF in Pakistani population. Methods This proof-of-concept, open label non-randomized clinical trial was conducted at a tertiary care cardiac center of Karachi, Pakistan. Patients with HFrEF were prescribed with Sacubitril/Valsartan and followed for 12 weeks for the assessment of safety and tolerability. Safety measures included incidence of hypotension, renal dysfunction, hyperkalemia, and angioedema. Results Among the 120 HFrEF patients, majority were male (79.2%) with means age of 52.73 ± 12.23 years. At the end of 12 weeks, four (3.3%) patients died and eight (6.7%) dropped out of the study. In the remaining 108 patients, 80.6% (87) of the patients were tolerant to the prescribed dose. Functional class improved gradually with 75.0% (81) in class I and 24.1% (26) in class II, and only one (0.9%) patient in class III at the end of 12 weeks. Hyperkalemia remains the main safety concern with incidence rate of 21.3% (23) followed by hypotension in 19.4% (21), and renal dysfunction in 3.7% (4) of the patients. Conclusions Sacubitril/Valsartan therapy in HFrEF patients is safe and moderately tolerated among the Pakistani population. It can be used as first line of treatment for these patients. Trial registration NCT05387967. Registered 24 May 2022—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT05387967

Transformation and many other substitution methods have been used to solve non-linear differential fractional equations. In this present work, the homotopy perturbation method to solve the non-linear differential fractional equation with the help of He’s Polynomials is provided as the transformation plays an essential role in solving differential linear and non-linear equations. Here is the α-Sumudu technique to find the relevant results of the gas dynamics equation in fractional order. To calculate the non-linear fractional gas dynamical problem, a consumer method created on the new homotopy perturbation a-Sumudu transformation method (HP TM) is suggested. In the Caputo type, the derivative is evaluated. a-Sumudu homotopy perturbation technique and He’s polynomials are all incorporated in the HPSaTM. The availability of He’s polynomials could be used to conveniently manage the non-linearity. The suggested approach shows that the strategy is simple to implement and provides results that can be compared to the results gained from any other transformation technique.

This paper presents a novel digital microfluidics platform that utilizes PCB substrate designed on Easy EDA software and is based on electrowetting on a dielectric (EWOD) phenomenon. For droplet actuation, the platform’s performance was examined at different DC voltages ranging from 300V to 450V. The fabrication process was made simple and inexpensive by using readily available, low-cost ingredients including silicone oil, cooking oil, and olive oil with grafting tape as a dielectric layer. Compared to other oils used for droplet actuation, cooking oil yields the highest droplet velocity. Due to its affordable and easy-to-fabricate nature, our suggested digital microfluidics platform will be feasible for droplet actuation and can also be applied to medical diagnostic applications like DNA analysis and cell culture, as well as the detection of environmental pollutants.

The impact of tilted angles on contact angles of water droplets in digital microfluidics was investigated. Experiments were conducted tilting the chip from 0 to 10 degrees at voltage increments of 50V from 250V to 400V DC. Both advancing and receding contact angles of the water droplets were measured at each angle and voltage combination. As the tilted angle increased from horizontal to 10 degrees, the advancing contact angle generally decreased whereas the receding contact angle increased. This trend held for all tested voltages. The changes were more pronounced at higher tilt angles above 5 degrees. Voltage was also found to influence the contact angles, with both advancing and receding angles decreasing with increasing driving voltage. The results provide insight into how tilted surface angles affect wetting properties in digital microfluidics. By understanding these relationships between contact angles, tilt angles and driving voltages, design parameters like maximum operational tilt angles before droplet pinning or instability can be better determined. The findings may assist in designing and optimizing tilted or three-dimensional digital microfluidic devices and applications.

This study examines the various ways that fractional Laplace transform can be used to solve three different kinds of mathematical equations: the equation of analysis of electric circuits, simultaneous differential equations, and the heat conduction equation. This article how to use the fractional Laplace transform to calculate heat flow in semi-infinite solids in the context of heat conduction. The answers that are developed offer important information about how temperatures vary across time and space. The essay also examines how to analyse electrical circuits using the Fractional Laplace transform. This method allows researchers to measure significant electrical parameters including charge and current, which improves their comprehension of circuit dynamics. Practical examples are included throughout the essay to show how useful the Fractional Laplace transform is in various fields. As a result of the answers found using this methodology, researchers and engineers working in the fields of heat conduction, system dynamics, and circuit analysis can gain important new knowledge. In conclusion, this study explains the applicability and effectiveness of the fractional Laplace transform in resolving a variety of mathematical equations. It is a vital tool for researchers because it may be used in a wide range of scientific and engineering areas.

Abstract 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.

Abstract 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 1H-NMR, 13C-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 (Ki 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.

Abstract A new series of N-thioacylated ciprofloxacin 3a–n were designed and synthesized based on Willgerodt–Kindler reaction. The results of in vitro urease inhibitory assay indicated that almost all the synthesized compounds 3a–n (IC50 = 2.05 ± 0.03–32.49 ± 0.32 μM) were more potent than standard inhibitors, hydroxyurea (IC50 = 100 ± 2.5 μM) and thiourea (IC50 = 23 ± 0.84 μM). The study of antibacterial activity against Gram-positive species (S. aureus and S. epidermidis) revealed that the majority of compounds were more active than ciprofloxacin as the standard drug, and 3h derivative bearing 3-fluoro group had the same effect as ciprofloxacin against Gram-negative bacteria (P. aeruginosa and E. coli). Based on molecular dynamic simulations, compound 3n exhibited pronounced interactions with the critical residues of the urease active site and mobile flap pocket so that the quinolone ring coordinated toward the metal bi-nickel center and the essential residues at the flap site like His593, His594, and Arg609. These interactions caused blocking the active site and stabilized the movement of the mobile flap at the entrance of the active site channel, which significantly reduced the catalytic activity of urease. Noteworthy, 3n also exhibited IC50 values of 5.59 ± 2.38 and 5.72 ± 1.312 µg/ml to inhibit urease enzyme against C. neoformans and P. vulgaris in the ureolytic assay.

The integral transformations is a complicated function from a function space into a simple function in transformed space. Where the function being characterized easily and manipulated through integration in transformed function space. The two parametric form of SEE transformation and its basic characteristics have been demonstrated in this study. The transformed function of a few fundamental functions along with its time derivative rule is shown. It has been demonstrated how two parametric SEE transformations can be used to solve linear differential equations. This research provides a solution to population growth rate equation. One can contrast these outcomes with different Laplace type transformations

Abstract Background Cancer is the most cause of morbidity and mortality, and a major public health problem worldwide. In this context, two series of quinazolinone 5a–e and dihydroquinazolinone 10a–f compounds were designed, synthesized as cytotoxic agents. Methodology All derivatives (5a–e and 10a–f) were synthesized via straightforward pathways and elucidated by FTIR, 1H-NMR, CHNS elemental analysis, as well as the melting point. All the compounds were evaluated for their in vitro cytotoxicity effects using the MTT assay against two human cancer cell lines (MCF-7 and HCT-116) using doxorubicin as the standard drug. The test derivatives were additionally docked into the PARP10 active site using Gold software. Results and discussion Most of the synthesized compounds, especially 5a and 10f were found to be highly potent against both cell lines. Synthesized compounds demonstrated IC50 in the range of 4.87–205.9 μM against HCT-116 cell line and 14.70–98.45 μM against MCF-7 cell line compared with doxorubicin with IC50 values of 1.20 and 1.08 μM after 72 h, respectively, indicated the plausible activities of the synthesized compounds. Conclusion The compounds quinazolinone 5a–e and dihydroquinazolinone 10a–f showed potential activity against cancer cell lines which can lead to rational drug designing of the cytotoxic agents.

A novel series of quinazoline-based agents bearing triazole-acetamides 8a-l were designed and synthesized. All the obtained compounds were tested for in vitro cytotoxic activities against three human cancer cell lines named HCT-116, MCF-7, and HepG2, as well as a normal cell line WRL-68 after 48 and 72 h. The results implied that quinazoline-oxymethyltriazole compounds exhibited moderate to good anticancer potential. The most potent derivative against HCT-116 was 8a (X = 4-OCH3 and R = H) with IC50 values of 10.72 and 5.33 μM after 48 and 72 h compared with doxorubicin with IC50 values of 1.66 and 1.21 μM, respectively. The same trend was seen in the HepG2 cancerous cell line in which 8a recorded the best results with IC50 values of 17.48 and 7.94 after 48 and 72 h, respectively. The cytotoxic analysis against MCF-7 showed that 8f with IC50 = 21.29 μM (48 h) exhibited the best activity, while compounds 8k (IC50 = 11.32 μM) and 8a (IC50 = 12.96 μM), known as the most effective cytotoxic agents after 72 h. Doxorubicin as positive control exhibited IC50 values of 1.15 and 0.82 μM after 48 and 72 h, respectively. Noteworthy, all derivatives showed limited toxicity against the normal cell line. Moreover, docking studies were also presented to understand the interactions between these novel derivatives and possible targets.

Abstract The present article describes the design, synthesis, in vitro urease inhibition, and in silico molecular docking studies of a novel series of nitrothiazolacetamide conjugated to different thioquinazolinones. Fourteen nitrothiazolacetamide bearing thioquinazolinones derivatives (8a-n) were synthesized through the reaction of isatoic anhydride with different amine, followed by reaction with carbon disulfide and KOH in ethanol. The intermediates were then converted into final products by treating them with 2-chloro-N-(5-nitrothiazol-2-yl)acetamide in DMF. All derivatives were then characterized through different spectroscopic techniques (1H, 13C-NMR, MS, and FTIR). In vitro screening of these molecules against urease demonstrated the potent urease inhibitory potential of derivatives with IC50 values ranging between 2.22 ± 0.09 and 8.43 ± 0.61 μM when compared with the standard thiourea (IC50 = 22.50 ± 0.44 μM). Compound 8h as the most potent derivative exhibited an uncompetitive inhibition pattern against urease in the kinetic study. The high anti-ureolytic activity of 8h was confirmed against two urease-positive microorganisms. According to molecular docking study, 8h exhibited several hydrophobic interactions with Lys10, Leu11, Met44, Ala47, Ala85, Phe87, and Pro88 residues plus two hydrogen bound interactions with Thr86. According to the in silico assessment, the ADME-Toxicity and drug-likeness profile of synthesized compounds were in the acceptable range.

Human activity recognition (HAR) is pivotal in advancing applications ranging from healthcare monitoring to interactive gaming. Traditional HAR systems, primarily relying on single data sources, face limitations in capturing the full spectrum of human activities. This study introduces a comprehensive approach to HAR by integrating two critical modalities: RGB imaging and advanced pose estimation features. Our methodology leverages the strengths of each modality to overcome the drawbacks of unimodal systems, providing a richer and more accurate representation of activities. We propose a two-stream network that processes skeletal and RGB data in parallel, enhanced by pose estimation techniques for refined feature extraction. The integration of these modalities is facilitated through advanced fusion algorithms, significantly improving recognition accuracy. Extensive experiments conducted on the UTD multimodal human action dataset (UTD MHAD) demonstrate that the proposed approach exceeds the performance of existing state-of-the-art algorithms, yielding improved outcomes. This study not only sets a new benchmark for HAR systems but also highlights the importance of feature engineering in capturing the complexity of human movements and the integration of optimal features. Our findings pave the way for more sophisticated, reliable, and applicable HAR systems in real-world scenarios. [ABSTRACT FROM AUTHOR]

Although green training has been shown in past research to promote environmentally responsible behaviors at work, scholars have paid less attention to its influence on employees' eco‐friendly behaviors outside of work. This omission is critical because confining green training research to the work domain obscures its benefits in promoting employees' pro‐environmental behaviors beyond the workplace, and thus its role in supporting organizational efforts to conserve the natural environment. To address this gap, we examine the direct and indirect (via connectedness to nature) relationships between green training and employees' eco‐friendly behaviors outside of work, including consumption of eco‐friendly products, reuse of items and materials, and reduced consumption of resources such as water, electricity, and paper. We also examine the moderating influence of intrinsic spirituality on the direct link between green training and connectedness to nature, as well as the indirect link between green training and eco‐friendly behaviors beyond the workplace. Using time‐lagged, multisource data, we find support for our hypotheses. Our findings advance knowledge on the important yet largely overlooked role of green training in shaping employees' environmentally responsible behaviors outside of the workplace. [ABSTRACT FROM AUTHOR]

Drawing on the depletion model of self-regulation, this study investigates how death anxiety depletes the energy of SLBs, resulting in negative consequences for their work drive and public service performance. The study also examines the importance of trait mindfulness as a boundary condition for determining whether the psychological and work-related outcomes of death anxiety are more or less severe for some SLBs. Using time-lagged and supervisor-matched data from 417 respondents, our findings provide new insights into SLBs' psychological response and job performance in the face of a life-threatening global pandemic. [ABSTRACT FROM AUTHOR]

The present study examines the role of death anxiety as an important mechanism underlying the relationship between fear of Covid-19 and hotel frontline employees' (FLEs) sense of work alienation. Importantly, the study proposes FLEs' intrinsic spirituality as being a relevant boundary condition. Results, based on time-lagged survey data (three rounds, 2 weeks apart) from 203 FLEs in 91 hotels and analyzed using structural equation modeling, reveal that death anxiety mediates the association between fear of Covid-19 and work alienation. In addition, FLEs' intrinsic spirituality moderates the direct relationship between fear of Covid-19 and death anxiety and the indirect relationship between fear of Covid-19 and work alienation, such that the relationships are weak when intrinsic spirituality is high (vs. low). The study offers several important suggestions that can help hospitality managers address FLEs' sense of work alienation during traumatic conditions. Highlights: Death anxiety mediates the relationship between fear of Covid-19 and work alienation. Intrinsic spirituality moderates the link between fear of Covid-19 and death anxiety. Intrinsic spirituality moderates the indirect fear of Covid-19-work alienation link. The findings can help hotel managers address FLEs' sense of work alienation. [ABSTRACT FROM AUTHOR]