Synthesis, in silico molecular docking analysis, pharmacokinetic properties and evaluation of antibacterial and antioxidant activities of fluoroquinolines

Background Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs. Methods 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier–Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina against E. coli DNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET. Results Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds 4, 5, 6, 7, 8, 10, 15, and 16 exhibited activity against E. coli, P. aeruginosa, S. aureus and S. pyogenes with IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 μg/mL. Compound 9 displayed IZ against three of the bacterial strains except S. aureus. The IC50 for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 μg/mL. The binding affinities of the synthesized compounds were from − 6.1 to − 7.2 kcal/mol against E. coli DNA gyrase B and − 6.8 to − 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski’s rule of five without violation. Conclusion Compounds 4, 5, 6, 7, 8, 10, 15, and 16 displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound 8 (13.6 ± 0.22 mm) showed better IZ against P. aeruginosa compared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds 5, 6, 7, 8, 9 and 10 showed comparable binding affinities in their in silico molecular docking analysis against E. coli DNA gyrase B. All of the synthesized compounds also obeyed Lipinski’s rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds 7 and 8 were proved to be a very potent radical scavenger with IC50 values of 5.31 and 5.41 μg/mL, respectively. Compound 5, 6, 8, 10 and 16 had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.

Kinetic control concept for the diffusion processes of paracetamol active molecules across affinity polymer membranes from acidic solutions

Background Paracetamol compound remains the most used pharmaceutical as an analgesic and antipyretic for pain and fever, often identified in aquatic environments. The elimination of this compound from wastewater is one of the critical operations carried out by advanced industries. Our work objective was to assess studies based on membrane processes by using two membranes, polymer inclusion membrane and grafted polymer membrane containing gluconic acid as an extractive agent for extracting and recovering paracetamol compound from aqueous solutions. Result The elaborated membrane characterizations were assessed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Kinetic and thermodynamic models have been applied to determine the values of macroscopic (P and J0), microscopic (D* and Kass), activation and thermodynamic parameters (Ea, ΔH#, ΔS#, ΔH#diss, and ΔH#th). All results showed that the PVA–GA was more performant than its counterpart GPM–GA, with apparent diffusion coefficient values (107D*) of 41.807 and 31.211 cm2 s−1 respectively, at T = 308 K. In addition, the extraction process for these membranes was more efficient at pH = 1. The relatively low values of activation energy (Ea), activation association enthalpy (ΔH≠ass), and activation dissociation enthalpy (ΔH≠diss) have indicated a kinetic control for the oriented processes studied across the adopted membranes much more than the energetic counterpart. Conclusion The results presented for the quantification of oriented membrane process ensured clean, sustainable, and environmentally friendly methods for the extraction and recovery of paracetamol molecule as a high-value substance.

Solvothermal synthesis of pure and Sn-doped Bi2S3 and the evaluation of their photocatalytic activity on the degradation of methylene blue

Background A large volume of dye molecules finds its way into the environment, accumulates in water bodies, and makes the aquatic system unsafe to human health. Due to the complex nature of these dye materials, most of the conventional techniques are not effective for their removal. Semiconductor photocatalysis has emerged as a promising technique for the destruction of organic pollutants under UV or visible light irradiation. Among the semiconductors, Bi2S3 is widely employed in photocatalysis due to its non-toxicity and chemical stability. However, one of its problems is the high recombination rate of the charge, and various methods have been employed to enhance the photo-reactivity. One of these methods is the incorporation of transition elements. Results Herein, a facile solvothermal method was used to prepare Bi2S3 nanorods and needle- shaped Sn doped Bi2S3, using bismuth(III) tris(N-phenyldithiocarbamate) as a single-source precursor. The prepared nanomaterials were characterized, and used as efficient photocatalyst for the photo enhanced degradation of methylene blue (MB) dye under visible light irradiation. The nanomaterials exhibited very good photocatalytic activity towards the photo degradation of MB, showing a degradation rate of up to 83% and 94% within 150 min for the pristine and Sn doped Bi2S3, respectively. Conclusion The enhancement in the photocatalytic activity of the Sn doped Bi2S3 was attributed to the suppression in the recombination rate of the electron‐hole pairs, due to the formation of new energy level below the CB, that was capable of altering the equilibrium concentration of the carrier. This confirmed that Sn doped Bi2S3 could be utilized as valuable cost-efficient catalysts for eliminating methyl blue from aqueous solutions and also possible candidates in environmental pollution treatment.

Inonotus obliquus polysaccharide ameliorates serum profiling in STZ-induced diabetic mice model

Background Diabetes mellitus is a systemic disease mainly caused by the disorder of metabolism, which has become huge threat to human health. Polysaccharides are the main active substance from Inonotus obliquus (I. obliquus) with hypoglycemic effect. This study aims to evaluate the hypoglycemic activity and investigate the molecular mechanism of I. obliquus polysaccharide (IOP) in streptozotocin (STZ)-induced diabetic mice using metabolomics based on UPLC-Q-Exactive-MS method. Results The results showed that the oral administration of IOP in high dose (1.2 g/kg) can significantly reduce the blood glucose with 31% reduction comparing with the diabetic model and relieve dyslipidemia in diabetic mice. By UPLC-Q-Exactive-MS method and multivariate statistical analysis, a total of 15 differential metabolites were identified, including 4 up-regulated and 11 down-regulated biomarkers, of which l-tryptophan, l-leucine, uric acid, 12-HETE, arachidonic acid, PC(20:1(11Z)/14:1(9Z)) and SM(d18:0/24:1(15Z)) were exhibited an important variation, as the potential biomarkers in diabetes. Pathway analysis indicated that phenylalanine, tyrosine and tryptophan biosynthesis and arachidonic acid metabolism were prone to interference in diabetes. Moreover, leucine and proline were reversed and phytosphingosine was further reduced in diabetic mice under the intervention of IOP. Conclusion IOP has predominant hyperglycemic effect on STZ-induced diabetic mice via ameliorating serum profiling.

Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines

Background Liver cancer is predicted to be the sixth most diagnosed cancer globally and fourth leading cause of cancer deaths. In this study, a series of indole-3-isoxazole-5-carboxamide derivatives were designed, synthesized, and evaluated for their anticancer activities. The chemical structures of these of final compounds and intermediates were characterized by using IR, HRMS, 1H-NMR and 13C-NMR spectroscopy and element analysis. Results The cytotoxic activity was performed against Huh7, MCF7 and HCT116 cancer cell lines using sulforhodamine B assay. Some compounds showed potent anticancer activities and three of them were chosen for further evaluation on liver cancer cell lines based on SRB assay and real-time cell growth tracking analysis. Compounds were shown to cause arrest in the G0/G1 phase in Huh7 cells and caused a significant decrease in CDK4 levels. A good correlation was obtained between the theoretical predictions of bioavailability using Molinspiration calculation, Lipinski’s rule of five, and experimental verification. These investigations reveal that indole-isoxazole hybrid system have the potential for the development of novel anticancer agents. Conclusions This study has provided data that will form the basis of further studies that aim to optimize both the design and synthesis of novel compounds that have higher anticancer activities.

n-Heptane isomerization activities of Pt catalyst supported on micro/mesoporous composites

Pt loaded on a series of MCM-48 silica and composites with HZSM-5 zeolite, HY zeolite, or TiO2 has been prepared and studied for n-heptane isomerization reaction at 200–350 °C. The structural characterization, acid distribution, and morphology of these catalysts were characterized by X-ray diffraction, Fourier transform infrared, UV–Vis diffuse reflectance, scanning electron microscope, temperature-programmed desorption of NH3, and nitrogen adsorption–desorption methods. The results show that these catalysts have a good selectivity to multi branched isomers, while producing low aromatic compounds. Also, these new composite catalysts prove the catalytic stability during the time of reaction. The most desirable results, and significantly higher n-heptane conversion and isomerization selectivity were achieved with Pt/MCM48-HZSM5 catalyst.

A new LC–MS/MS method for multiple residues/contaminants in bovine meat

A multi-class and multi-residue/contaminant method for the determination of veterinary drug and pesticide residues and mycotoxins in bovine meat has been developed and validated. The veterinary drug residues/contaminants included antimicrobials, anabolic hormones, lactones, β-agonists, mycotoxins, and pesticides. Isotopic labeled internal standards were included to compensate residual matrix effects. The calibrators used in the method demonstrated linearity with the R2 > 0.98. The decision limit (CCα) values were in the range from 0.067 to 2103.84 μg/kg, while the range for detection capability (CCβ) was from 0.083 to 2482.13 μg/kg. The limit of detection (LOD) and limit of quantification (LOQ) were in the range from 0.059 to 291.36 μg/kg, and 0.081 to 328.13 μg/kg, respectively. The recovery of analytes ranged from 61.28% to 116.20%. The intra-day coefficient of variation (CV) was from 0.97 to 25.93% and the inter-day CV was 2.30–34.04%. The method has been used for the determination of 49 residues/contaminants in bovine meat. Application of the method in routine analysis in bovine samples, revealed in limited samples the presences of enrofloxacin, oxytetracycline and sulfadiazine at the concentration of 35.22 µg/kg, 27.35 µg/kg, and 36.20 µg/kg, respectively.

Synthesis, antibacterial and antioxidant activities of Thiazole-based Schiff base derivatives: a combined experimental and computational study

Background Thiazole-based Schiff base compounds display significant pharmacological potential with an ability to modulate the activity of many enzymes involved in metabolism. They also demonstrated to have antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. In this work, conventional and green approaches using ZnO nanoparticles as catalyst were used to synthesize thiazole-based Schiff base compounds. Results Among the synthesized compounds, 11 showed good activities towards Gram-negative E. coli (14.40 ± 0.04), and Gram-positive S. aureus (15.00 ± 0.01 mm), respectively, at 200 μg/mL compared to amoxicillin (18.00 ± 0.01 mm and 17.00 ± 0.04). Compounds 7 and 9 displayed better DPPH radical scavenging potency with IC50 values of 3.6 and 3.65 μg/mL, respectively, compared to ascorbic acid (3.91 μg/mL). The binding affinity of the synthesized compounds against DNA gyrase B is within − 7.5 to − 6.0 kcal/mol, compared to amoxicillin (− 6.1 kcal/mol). The highest binding affinity was achieved for compounds 9 and 11 (− 6.9, and − 7.5 kcal/mol, respectively). Compounds 7 and 9 displayed the binding affinity values of − 5.3 to − 5.2 kcal/mol, respectively, against human peroxiredoxin 5. These values are higher than that of ascorbic acid (− 4.9 kcal/mol), in good agreement with the experimental findings. In silico cytotoxicity predictions showed that the synthesized compounds Lethal Dose (LD50) value are class three (50 ≤ LD50 ≤ 300), indicating that the compounds could be categorized under toxic class. Density functional theory calculations showed that the synthesized compounds have small band gap energies ranging from 1.795 to 2.242 eV, demonstrating that the compounds have good reactivities. Conclusions The synthesized compounds showed moderate to high antibacterial and antioxidant activities. The in vitro antibacterial activity and molecular docking analysis showed that compound 11 is a promising antibacterial therapeutics agent against E. coli, whereas compounds 7 and 9 were found to be promising antioxidant agents. Moreover, the green synthesis approach using ZnO nanoparticles as catalyst was found to be a very efficient method to synthesize biologically active compounds compared to the conventional method.

Chromium-based metal organic framework for pipette tip micro-solid phase extraction: an effective approach for determination of methyl and propyl parabens in wastewater and shampoo samples

Background A chromium-based metal organic framework was synthesized and employed as an efficient sorbent for pipette tip micro-solid phase extraction and preconcentration of parabens from wastewater and shampoo samples up to sub-ppb level before their spectrophotometric analysis. Results Factors affecting preconcentration including volume and type of solvent, amount of sorbent, number of extraction, and volume and pH of samples were optimized employing one-variable-at-a-time and response surface methodology. Obtained analytical characteristics of the method proves its usefulness for analysis of real samples. Linear range of the method for parabens was 1.0–200.0 μg/L. Detection limit of the protocol was 0.24 µg/L for propyl paraben and 0.25 µg/L for methyl paraben. Reproducibility of the protocol defined as % RSD was better than 5.78%. Synthesized adsorbent can be re-used for at least 20 extractions. Conclusion The method showed a good detection limit and precision for determination of methyl- and propyl-paraben in wastewater and shampoo samples.