Copper supported modified magnetic carrageenan as a bio-based catalyst for the synthesis of novel scaffolds bearing the 1,2,3-triazole unit through the click reaction.

The ongoing work delineates the design of a novel library of 1,2,3-triazole-attached phenylacetamides through molecular hybridization of propargyl and phenylacetamide derivatives. Copper-supported modified magnetic carrageenan serves as a green heterogeneous catalyst, ensuring high yield, efficient reaction times, high atom economy, utilization of an environmentally friendly catalyst from a natural source, and a straightforward workup procedure. The successful synthesis of the catalyst is confirmed and evaluated using various analytical techniques, while the synthetic compounds are characterized through 1H NMR and 13C NMR.

Evaluation of novel 2-(quinoline-2-ylthio)acetamide derivatives linked to diphenyl-imidazole as α-glucosidase inhibitors: Insights from in silico, in vitro, and in vivo studies on their anti-diabetic properties.

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 IC50 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 (IC50 = 0.180 µM) demonstrated the highest potency and revealed a competitive inhibitory mechanism in kinetic studies (Ki = 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.

Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure-activity relationship studies.

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.

Alpha-glucosidase inhibitory and hypoglycemic effects of imidazole-bearing thioquinoline derivatives with different substituents: In silico, in vitro, and in vivo evaluations.

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 (IC50 = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with Ki = 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.

The effect of essential oil of Zataria multiflora incorporated chitosan (free form and Pickering emulsion) on microbial, chemical and sensory characteristics in salmon (Salmo trutta).

The objective of current research was to prepare a new biodegradable coating containing chitosan (Ch) and zataria multiflora essential oil (ZMEO) (free and Pickering emulsion (PEO) forms), in order to enhance the Salmo trutta shelf life. Our results showed, the mean of films thickness, mechanical properties (elastic modulus (EM) and tensile strength (TS) analysis) and WVP in different treatments were ranged from 0.103 ± 0.003 (for Ch) to 0.109 ± 0.003 (for Ch-PEO (2.5 %)) µm for thickness, from 3.2 ± 1.6 (for Ch) to 8.15 ± 2.3 (for Ch-EO) MPa for EM, from 1.3 ± 0.5 (for Ch-EO) to 1.6 ± 0.06 (for Ch) Mpa for TS and from 0.1 ± 0.02 (for Ch) to 0.8 ± 0.05 (for Ch-EO) (×10 - 11(g m/m2 s Pa) for WVP. In current research, the lowest and highest total viable counts (TVC) was related to Ch-PEO (1.7 log CFU/g) and control treatments (4.65 log CFU/g). The lowest and highest of pH was related to the Ch-PEO (6.45) and the control (7.1), the lowest and highest of PV (peroxide value) was related to Ch-PEO (0.34 meq/kg) and control treatment (1.37 meq/kg), the lowest and highest of TBARS (thiobarbituric acid reactive substances) was related to Ch-PEO (0.37 mg/kg) and control treatment (2.23 mg/kg) and also the lowest and highest of TVB-N (total volatile base nitrogen) was related to Ch-PEO (17.7 mg) and control (59 mg). Also, Ch-PEO showed the best sensory properties after sixteen days. Among all the treatments in all the tests, the best maintenance property was related to the Ch-PEO, therefore, chitosan coatings containing ZM Pickering emulsion should be considered as a potential active coating in the fish industry.

Environmentally friendly catalyst- and solvent-free synthesis of 2-anilino nicotinic acids derivatives as potential lead COX inhibitors.

In this study, an environmentally friendly, solvent- and catalyst-free synthesis of 2-anilino nicotinic acids derivatives is reported. This operationally simple and green procedure was applied to a selection of primary aromatic amines giving rise to 23 derivatives of 2-anilino nicotinic acids in a very short reaction time (15-120 min) with good to excellent yield. Next, similarity searches were executed on these derivatives to find the possible biological target. These products were screened for inhibition of COX-1 and COX-2 by molecular docking and dynamic studies. In silico studies revealed that among these derivatives, the structure 10 bearing meta-chlorine substitutions could act as COX-1 and COX-2 inhibitors. These results can be used in designing important lead compounds for further development as potential anti-inflammatory drugs.

Preparation of agar functionalized graphene oxide-immobilized copper ferrite aerogel for dye degradation via dark-Fenton oxidative process.

Dye and textile industries are one of the main causes of water pollution and put the environment and health of society at risk. Developing new materials to decontaminate industrial waste effluents containing dyes as pollutants is challenging due to numerous issues, including tailoring recyclable and biodegradable agents. This study focuses on applying an advanced oxidation process, electro-Fenton for the treatment of dye-containing wastewater using agar-functionalized graphene oxide-immobilized copper ferrite aerogel. The objective is therefore to determine the optimal conditions for the degradation of model pollutants methylene blue (MB). MB was oxidized and degraded through the dark-Fenton process using Agar@GO-CuFe2O4 as a new biobased catalyst. The effect of the operating parameters was then evaluated to determine the optimal conditions. The degradation process was screened for different initial concentrations of dye solution between 10 and 150 mg/l, a volume range of H2O2 between 0.5 and 2.5 ml, and different pH from 2 to 7. The results show that 99.89 % of the MB with the initial concentration of 150 ppm was degraded by 20 mg of the catalyst and 2 ml of H2O2 (30 % W/W) at 40 °C and pH = 6. Pseudo-second-order kinetics satisfactorily describes the experimental data. SYNOPSIS: The prepared catalyst can be applied to oxidize industrial effluents before they are released into the environment.

Phenyl-quinoline derivatives as lead structure of cholinesterase inhibitors with potency to reduce the GSK-3ß level targeting Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that leads to cognitive decline and memory loss. Unfortunately, there is no effective treatment for this condition, so there is a growing interest in developing new anti-AD agents. In this research project, a series of phenyl-quinoline derivatives were designed as potential anti-AD agents. These derivatives were substituted at two different positions on benzyl and phenyl rings. The structures of the derivatives were characterized using techniques such as IR spectroscopy, 1H NMR, 13C NMR, and elemental analysis. During the in vitro screening, the derivatives were tested against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was observed that most of the derivatives showed higher selectivity against BChE compared to AChE. Among the derivatives, analog 7n (with a methoxy group at R1 and a 4-bromine substituent at R2 exhibited the highest potency, with a 75-fold improvement in the activity compared to the positive control. Importantly, this potent analog demonstrated no toxicity at the tested concentration on SH-SY5Y cells, indicating its potential as a safe anti-AD agent. The level of GSK-3ß was also reduced after treatments with 7n at 50 µM. Overall, this study highlights the design and evaluation of phenyl-quinoline derivatives as promising candidates for developing novel anti-AD agents.

pH-responsive magnetic biocompatible chitosan-based nanocomposite carrier for ciprofloxacin release.

The pH-sensitive and magnetic-triggered release ensures the effective delivery of drugs. Chitosan carries amine pendants that encourage the fabrication of pH-responsive carriers. Montmorillonite (MMt), an attractive nano-clay in drug delivery possessing high encapsulation properties, was magnetized through the co-precipitation of Fe3+/Fe2+ ions. The study aimed to integrate the magnetic montmorillonite (mMMt) into the chitosan matrix and crosslinked by citric acid (CA) to achieve the nanocomposite carrier with double-responsive features for effective drug delivery. The release evaluation revealed that coating the mMMt with CA-crosslinked chitosan prevented the burst release of Ciprofluxcacin (Cip). The nanocomposite showed a high sustained release, and the release rate in the neutral environment (pH 7.4) was remarkably higher than in acidic media (pH 5.8). The new nanocomposite carrier showed high encapsulation efficiency to Cip (about 98 %). The study was developed by investigating external magnetic effects on the release rate, which lead to an increase in the release rate. The kinetics studies confirmed the diffusion mechanism for Cip release in all experimental media. The Cip-loaded nanocomposite carriers showed antibacterial activity against E. coli and S. aureus.

Synthesis, ADMT prediction, and in vitro and in silico α-glucosidase inhibition evaluations of new quinoline-quinazolinone-thioacetamides.

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.

[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as new therapeutic candidates against urease positive microorganisms: design, synthesis, pharmacological evaluations, and in silico studies.

Regarding the important role of the urease enzyme as a virulence factor in urease-positive microorganisms in this study, new series of [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives were designed and synthesized. All compounds evaluated against urease enzyme exhibiting IC50 values of 0.87 ± 0.09 to 8.32 ± 1.21 µM as compared with thiourea as the positive control (IC50 = 22.54 ± 2.34 µM). The kinetic evaluations of 6a as the most potent derivative recorded a competitive type of inhibition. Molecular dynamic simulations of the 6a derivative were also conducted, showing that 6a occupied the active site with closed state. Antimicrobial activities of all derivatives were performed, and 6f (R = 3-Cl), 6g (R = 4-Cl), and 6h (R = 3,4-diCl) analogs demonstrated significant antifungal activities with MIC values of 1, 2, and 0.5 µg/mL compared with fluconazole with MIC = 2 µg/mL. Synthesized analogs also exhibited potent urease inhibitory activities against C. neoformans (IC50 = 83.7-118.7 µg/mL) and P. mirabilis (IC50 = 74.5-113.7 µg/mL), confirming their urease inhibitory potential. The results demonstrated that the designed scaffold could be considered a suitable pharmacophore to develop potent urease inhibitors.

Pyrolyzed magnetic NiO/carbon-derived nanocomposite from a hierarchical nickel-based metal-organic framework with ultrahigh adsorption capacity.

Herein, a simple one-pot solvothermal approach is used to create magnetic porous carbon nanocomposites which obtained from a nickel-based metal-organic framework (Ni-MOF) and examined for their ability to uptake methyl orange (MO) dye. Derived carbons with exceptional porosity and magnetic properties were created during the different pyrolysis temperatures of Ni-MOF (700, 800, and 900 °C) under a nitrogen atmosphere. The black powders were given the names CDM-700, CDM-800, and CDM-900 after they were obtained. A variety of analysis methods, including FESEM, EDS, XRD, FTIR, VSM, and N2 adsorption-desorption were used to characterize as-prepared powders. Furthermore, adsorbent dosage, contact time, pH variation, and initial dye concentration effects was investigated. The maximum adsorption capacities were 307.38, 5976.35, 4992.39, and 2636.54 mg/g for Ni-MOF, CDM-700, CDM-800, and CDM-900, respectively, which show the ultrahigh capacity of the resulted nanocomposites compared to newest materials. The results showed that not only the crystallinity turned but also the specific surface area was increased about four times after pyrolyzing. The results showed that the maximum adsorption capacity of MO dye for CDM-700 was obtained at adsorbent dosage of 0.083 g/L, contact time of 60 min, feed pH of 3, and temperature of 45 °C. The Langmuir model has the best match and suggests the adsorption process as a single layer. According to the results of reaction kinetic studies using well-known models, the pseudo-second-order model (R2 = 0.9989) displayed high agreement with the experimental data. The synthesized nanocomposite is introduced as a promising superadsorbent for eliminating dyes from contaminated water due to strong recycling performance up to the fifth cycle.

Synthesis, in vitro inhibitor screening, structure-activity relationship, and molecular dynamic simulation studies of novel thioquinoline derivatives as potent α-glucosidase inhibitors.

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, 1H-NMR, 13C-NMR, ESI-MS and elemental analysis. Next, the α-glucosidase inhibitory activities of derivatives were also determined and all the synthesized compounds (IC50 = 14.0 ± 0.6-373.85 ± 0.8 µM) were more potent than standard inhibitors acarbose (IC50 = 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 Ki 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.

CuFe2O4@SiO2@L-arginine@Cu(I) as a new magnetically retrievable heterogeneous nanocatalyst with high efficiency for 1,4-disubstituted 1,2,3-triazoles synthesis.

A novel magnetic heterogeneous catalyst was synthesized through the immobilization of copper ions onto the l-arginine functionalized CuFe2O4@SiO2. The prepared catalyst was characterized by Fourier Transform Infrared (FT-IR), X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), and Energy Dispersive X-Ray spectroscopy (EDX). The resulting catalyst was used in the ultrasonic-assisted synthesis of 1,2,3-triazoles via a one-pot three-component reaction of alkynes, alkyl halides, and sodium azides under green conditions within a short time. The catalyst reusability was investigated after five cycles and no significant loss of activity was observed.

Effective CO2 Capture and Selective Photocatalytic Conversion into CH3OH by Hierarchical Nanostructured GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg.

The attenuation of greenhouse gases, especially CO2, as one of the main causes of global warming and their conversion into valuable materials are among the challenges that must be met in the 21st century. For this purpose, hierarchical ternary and quaternary hybrid photocatalysts based on graphene oxide, TiO2, Ag2O, and arginine have been developed for combined CO2 capture and photocatalytic reductive conversion to methanol under visible and UV light irradiation. The material's band gap energy was estimated from the diffuse reflectance spectroscopy (DRS) Tauc analysis algorithm. Structural and morphological properties of the synthesized photocatalysts were studied using various analytical techniques such as Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The calculated band gaps for GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg were 3.18 and 2.62 eV, respectively. This reduction in the band gap showed that GO-TiO2-Ag2O-Arg has a significant visible light photocatalytic ability. The investigation of CO2 capture for the designed catalyst showed that GO-TiO2-Ag2O-Arg and GO-TiO2-Ag2O have high CO2 absorption capacities (1250 and 1185 mmol g-1, respectively, at 10 bar and 273 K under visible light irradiation). The amounts of methanol produced by GO-TiO2-Ag2O and GO-TiO2-Ag2O-Arg were 8.154 and 5.1 µmol·gcat1·h-1 respectively. The main advantages of this study are the high efficiencies and selectivity of catalysts toward methanol formation. The reaction mechanism to understand the role of hybrid photocatalysts for CO2 conversion is deliberated. In addition, these catalysts remain stable during the photocatalytic process and can be used repeatedly, proving to be enlightening for environmental research.

Multi-responsive chitosan-based hydrogels for controlled release of vincristine.

As medical research progresses, the derivation and development of biological materials such as hydrogels have steadily gained more interest. The biocompatibility and non-toxicity of chitosan make chitosan hydrogels potential carriers for drug delivery. This work aims to develop two multi-reactive, safe, and highly swellable bio-hydrogels consisting of chitosan-graft-glycerol (CS-g-gly) and carboxymethyl chitosan-graft-glycerol (CMCS-g-gly), for sustained and controlled drug release, improved bioavailability along with entrapment in nanocarriers, which reduces side effects of vincristine sulphate. CS-g-gly and CMCS-g-gly are successfully prepared and fully characterized using analytical techniques. Under various conditions, the prepared hydrogels exhibit a high swelling ratio. Vincristine-loaded CS-g-gly (VCR/CS-g-gly), and CMCS-g-gly (VCR/CMCS-g-gly) show high encapsulation efficiency between 72.28-89.97%, and 56.97-71.91%, respectively. VCR/CS-g-gly show a sustained release behavior, and the maximum release of VCR from hydrogels reached 82% after 120 h of incubation. MCF-7 (breast cancer cell line) and MCF-10 (normal breast cell line) are evaluated for cell viability and apoptosis induction. The in-vitro anti-tumor efficacy is investigated using flow cytometry. The tetrazolium-based MTT assay of hydrogels shows no evidence of significant cytotoxicity in MCF-7 and MCF-10 cells. According to these findings, these hydrogels can effectively deliver drugs to MCF-7 and other breast cancer cells.

Thermal insulation properties of lightweight, self-healing, and mesoporous carrageenan/PMMA cryogels.

The development of new bio-based cryogel materials with low environmental impact and various properties such as self-healing, flame-retardancy, low thermal conductivity has emerged as a cutting-edge research topic in special-purpose materials and a significant challenge. Herein, we report a simple processing methodology for preparing new mesoporous light weight thermal insulation biomass hybrid cryogels based on natural and biocompatible polymers, including marine glycosaminoglycan carrageenan moss (CM) and polymethyl methacrylate (PMMA) abbreviated as CM/PMMA under cryo conditions. The mechanical, thermal, and physicochemical characterization of the obtained hybrid cryogel was studied. The effect of increasing thickness on thermal conductivity and compressive strength was investigated. The results show that the thermal conductivity increases from 0.068 W m-1 K-1 to 0.124 W m-1 K-1 with increasing thickness. Also, the compressive strength changed from 89.5% MPa to 95.4% MPa. The results revealed that cryogel has a wrinkled surface and interconnected pores and exhibits high flexibility, self-healing ability, flame retardancy, and low thermal conductivity.

New thioxothiazolidinyl-acetamides derivatives as potent urease inhibitors: design, synthesis, in vitro inhibition, and molecular dynamic simulation.

To identify potent urease inhibitors, in the current study, a series of thioxothiazolidinyl-acetamides were designed and synthesized. The prepared compounds were characterized by spectroscopic techniques, including FTIR, 1HNMR, 13CNMR, and elemental analysis. In the enzymatic assessments, it was demonstrated that all derivatives had significant urease inhibition with IC50 values in the range of 1.473-9.274 µM in comparison with the positive control hydroxyurea (IC50 = 100.21 ± 2.5 µM) and thiourea (IC50 = 23.62 ± 0.84 µM). Compound 6i (N-benzyl-3-butyl-4-oxo-2-thioxothiazolidine-5-carboxamide) was the most active agent with an IC50 value of 1.473 µM. Additionally, kinetic investigation and in silico assessments of 6i was carried out to understand the type of inhibition and behavior of the most potent derivative within the binding site of the enzyme. Noteworthy, the anti-urease assay against P. vulgaris revealed 6e and 6i as the most active agents with IC50 values of 15.27 ± 2.40 and 17.78 ± 3.75 µg/mL, respectively. Antimicrobial evaluations of all compounds reveal that compounds 6n and 6o were the most potent antimicrobial agents against the standard and resistant S. aureus. 6n and 6o also showed 37 and 27% inhibition in the development of biofilm by S. aureus at 512 µg/ml. Furthermore, the MTT test showed no toxicity up to 100 µM. Taken together, the study suggests that the synthesized thioxothiazolidinyl-acetamides bases derivatives may serve as potential hits as urease inhibitors.

Palladium supported magnetic Fucus Vesiculosus extract as a natural and novel catalyst for the synthesis of N-alkyl-2-(4-methyl-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamide derivatives.

In this paper, a novel catalyst is introduced based on the immobilization of palladium onto magnetic Fucus Vesiculosus extract (Pd@mFuVe catalyst). For the synthesis of Pd@mFuVe catalyst, Fucus Vesiculosus extract is obtained from the plant source, followed by the synthesis of superparamagnetic iron oxide nanoparticles (SPION) onto the extract. The catalyst is characterized by several methods, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), FT-IR spectroscopy, vibrating sample magnetometer (VSM), powder X-ray diffraction analysis (XRD), and inductively coupled plasma (ICP). The activity of Pd@mFuVe catalyst is studied in the synthesis of N-alkyl-2-(4-methyl-1-oxoisoquinolin-2(1H)-yl)-2-phenylacetamides. The products were synthesized in three steps, the synthesis of 2-iodobenzoic acid from 2-aminobenzoic acid, which participated in a multicomponent reaction with allylamine, aldehydes, and isocyanides, followed by a cyclization reaction, catalyzed by Pd@mFuVe catalyst. The product yields are high and the catalyst showed good reusability after 5 sequential runs. The most significant, Pd@mFuVe catalyst is fabricated from a plant extract source as a green support for the catalyst.

Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.Communicated by Ramaswamy H. Sarma.