Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer's, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions.

In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a-f, 6a-f, and 7a-f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer's, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a-f, 6a-f, and 7a-f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents.

Based on previous developments of our research programs in trying to find new compounds with multiple biological targets such as antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic agents. In the context, a novel series of sulfonamide derivatives based on the pyrazole or pyridine moieties 3a, b, 7-9, 11-13, 15a, b, and 16 were synthesized from amine compounds with sulfonyl chloride derivatives. The structures of sulfonamide derivatives were elucidated via spectroscopy (1H and 13C NMR). The sulfonamide derivatives were biologically assessed in vitro for their anti-diabetic (α-amylase and α-glucosidase inhibition) and anti-Alzheimer's (acetylcholinesterase inhibition) activities. The biological results revealed that compound 15a is a powerful enzyme inhibitor for α-amylase and α-glucosidase. Also, compound 15b demonstrated inhibitor activity against the acetylcholinesterase enzyme. The structure-activity relationship study of sulfonamide derivatives was accomplished. Furthermore, complementary in silico molecular properties, drug-likeness, ADMET prediction, and surface properties of the two more powerful derivatives 15a and 15b were fulfilled and computed. These studies recommend 15a and 15b as candidates with modifications in their structures before the in vivo assays.

In vitro biological studies and computational prediction-based analyses of pyrazolo[1,5-a]pyrimidine derivatives.

There is a need for new pharmaceutical discoveries from bioactive nitrogenous derivatives due to the emergence of scourges, numerous pandemics, and diverse health problems. In this context, pyrazolo[1,5-a]pyrimidine derivatives 12a and 12b were synthesized and screened to evaluate their biological potentials in vitro as antioxidants, anti-diabetics, anti-Alzheimer's, anti-arthritics, and anti-cancer agents. Additionally, the computational pharmacokinetic and toxicity properties of the two pyrazolo[1,5-a]pyrimidines 12a and 12b were calculated and analyzed. The preliminary studies and results of this work represent the initial steps toward more advanced studies and define the bioactive chemical structure of pyrazolo[1,5-a]pyrimidine derivatives with the goal of exploring new drugs to address numerous health problems.

Removal of organic micropollutants in biologically active filters: A systematic quantitative review of key influencing factors.

Biofiltration utilizes natural mechanisms including biodegradation and biotransformation along with other physical processes for the removal of organic micropollutants (OMPs) such as pharmaceuticals, personal care products, pesticides and industrial compounds found in (waste)water. In this systematic review, a total of 120 biofiltration studies from 25 countries were analyzed, considering various biofilter configurations, source water types, biofilter media and scales of operation. The study also provides a bibliometric analysis to identify the emerging research trends in the field. The results show that granular activated carbon (GAC) either alone or in combination with another biofiltration media can remove a broad range of OMPs efficiently. The impact of pre-oxidation on biofilter performance was investigated, revealing that pre-oxidation significantly improved OMP removal and reduced the empty bed contact time (EBCT) needed to achieve a consistently high OMP. Biofiltration with pre-oxidation had median removals ranging between 65% and >90% for various OMPs at 10-45 min EBCT with data variability drastically reducing beyond 20 min EBCT. Biofiltration without pre-oxidation had lower median removals with greater variability. The results demonstrate that pre-oxidation greatly enhances the removal of adsorptive and poorly biodegradable OMPs, while its impact on other OMPs varies. Only 19% of studies we reviewed included toxicity testing of treated effluent, and even fewer measured transformation products. Several studies have previously reported an increase in effluent toxicity because of oxidation, although it was successfully abated by subsequent biofiltration in most cases. Therefore, the efficacy of biofiltration treatment should be assessed by integrating toxicity testing into the assessment of overall removal.

In Vitro Evaluation and Bioinformatics Analysis of Schiff Bases Bearing Pyrazole Scaffold as Bioactive Agents: Antioxidant, Anti-Diabetic, Anti-Alzheimer, and Anti-Arthritic.

In continuation of our research programs for the discovery, production, and development of the pharmacological activities of molecules for various disease treatments, Schiff bases and pyrazole scaffold have a broad spectrum of activities in biological applications. In this context, this manuscript aims to evaluate and study Schiff base-pyrazole molecules as a new class of antioxidant (total antioxidant capacity, iron-reducing power, scavenging activity against DPPH, and ABTS radicals), anti-diabetic (α-amylase% inhibition), anti-Alzheimer's (acetylcholinesterase% inhibition), and anti-arthritic (protein denaturation% and proteinase enzyme% inhibitions) therapeutics. Therefore, the Schiff bases bearing pyrazole scaffold (22a, b and 23a, b) were designed and synthesized for evaluation of their antioxidant, anti-diabetic, anti-Alzheimer's, and anti-arthritic properties. The results for compound 22b demonstrated significant antioxidant, anti-diabetic (α-amylase% inhibition), and anti-Alzheimer's (ACE%) activities, while compound 23a demonstrated significant anti-arthritic activity. Prediction of in silico bioinformatics analysis (physicochemical properties, bioavailability radar, drug-likeness, and medicinal chemistry) of the target derivatives (22a, b and 23a, b) was performed. The molecular lipophilicity potential (MLP) of the derivatives 22a, b and 23a, b was measured to determine which parts of the surface are hydrophobic and which are hydrophilic. In addition, the molecular polar surface area (PSA) was measured to determine the polar surface area and the non-polar surface area of the derivatives 22a, b and 23a, b. This study could be useful to help pharmaceutical researchers discover a new series of potent agents that may act as an antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic.

Seawater biodesalination treatment using Phormidium keutzingianum in attached growth-packed bed continuous flow stirred tank reactor.

Water scarcity is increasing worldwide due to rising population which is creating opportunities to unlock alternative green desalination techniques for seawater, such as biodesalination. Therefore, this study presents the utilization of the Phormidium keutzingianum strain in an attached growth-packed bed reactor to treat seawater in real-time in a continuous-flow stirred tank reactor for biodesalination. Two reactors were designed and developed, in which zeolites were used as the support media for the attached growth. The experiment was conducted in an open outdoor environment with a continuous air flow rate of 3 mL/min and two hydraulic retention times (HRT) of 7 and 15 d. Parameters such as the pH, chloride ion concentration, total organic carbon (TOC), and optical density were monitored regularly. The pH change was not significant in either reactor and remained within the range of 7.25-8.0. Chloride ion removal was the most crucial component of biodesalination efficiency, with d 7 removal efficiencies of approximately 40% and 32% for reactors 1 and 2, respectively. Reactor 1 exhibited a TOC reduction of 36% within the first 10 d at a HRT of 7, and when the HRT was set to 15 d, a TOC removal efficiency of 89% was achieved on d 53. For reactor 2, a TOC removal efficiency of approximately 81% was achieved on d 11 at HRT 7, and it reduced to less than 50% at an HRT of 15. The chloride ion and TOC removal phenomena were similar in both reactors. The optical density (OD) showed low measurement recordings, ranging from 0.005 to 0.01, indicating low cell detachment in the seawater effluent. Therefore, using the attached growth method for the biodesalination of seawater is feasible. Furthermore, biomass harvesting in attached growth systems is easier than that in suspension growth systems.

Exploring novel derivatives of isatin-based Schiff bases as multi-target agents: design, synthesis, in vitro biological evaluation, and in silico ADMET analysis with molecular modeling simulations.

Recently, scientists developed a powerful strategy called "one drug-multiple targets" to discover vital and unique therapies to fight the most challenging diseases. Novel derivatives of isatin-based Schiff bases 2-7 have been synthesized by the reaction of 3-hydrazino-isatin (1) with aryl aldehydes, hetero-aryl aldehydes, and dialdehydes. The structure of the synthesized derivatives was proved by physical and spectral analysis. Additionally, in vitro biological studies were performed, including antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic activities. The four derivatives 3b, 5a, 5b, and 5c possess the highest activities. Among the four potent derivatives, compound 5a exhibited the highest antioxidant (TAC = 68.02 ± 0.15 mg gallic acid per g; IRP = 50.39 ± 0.11) and scavenging activities (ABTS = 53.98 ± 0.12% and DPPH = 8.65 ± 0.02 µg mL-1). Furthermore, compound 5a exhibited an α-amylase inhibitory percentage of 57.64 ± 0.13% near the acarbose (ACA = 69.11 ± 0.15%) and displayed inhibitor activity of the acetylcholinesterase (AChE) enzyme = 36.38 ± 0.08%. Moreover, our work extended to determining the anti-arthritic effect, and compound 5a revealed good inhibitor activities with very close values for proteinase denaturation (PDI) = 39.59 ± 0.09% and proteinase inhibition (PI) = 36.39 ± 0.08%, compared to diclofenac sodium PDI = 49.33 ± 0.11% and PI = 41.88 ± 0.09%. Additionally, the quantum chemical calculations, including HOMO, LUMO, and energy band gap were determined, and in silico ADMET properties were predicted, and their probability was recorded. Finally, molecular docking simulations were performed inside α-amylase and acetylcholinesterase enzymes.

In vitro enzymatic evaluation of some pyrazolo[1,5-a]pyrimidine derivatives: Design, synthesis, antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic activities with molecular modeling simulation.

The strategy of utilizing nitrogen compounds in various biological applications has recently emerged as a powerful approach to exploring novel classes of therapeutics to face the challenge of diseases. A series of pyrazolo[1,5-a]pyrimidine-based compounds 3a-l and 5a-f were prepared by the direct cyclo-condensation reaction of 5-amino-1H-pyrazoles 1a, b with 2-(arylidene)malononitriles and 3-(dimethylamino)-1-aryl-prop-2-en-1-ones, respectively. The structures of the new pyrazolo[1,5-a]pyrimidine compounds were confirmed via spectroscopic techniques. The in vitro biological activities of all pyrazolo[1,5-a]pyrimidines 3a-l and 5a-f were evaluated by assaying total antioxidant capacity, iron-reducing power, the scavenging activity against 1-diphenyl-2-picryl-hydrazyl (DPPH) and 2, 2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, anti-diabetic, anti-Alzheimer, and anti-arthritic biological activities. All compounds displayed good to potent bioactivity, and three compounds 3g, 3h, and 3l displayed the most active derivatives. Among these derivatives, compound 3l exhibited the highest antioxidant (total antioxidant capacity [TAC] = 83.09 mg gallic acid/g; iron-reducing power [IRP] = 47.93 µg/ml) and free radicals scavenging activities with (DPPH = 18.77 µg/ml; ABTS = 40.44%) compared with ascorbic acid (DPPH = 4.28 µg/ml; ABTS = 38.84%). Furthermore, compound 3l demonstrated the strongest inhibition of α-amylase with a percent inhibition of 72.91 ± 0.14 compared to acarbose = 67.92 ± 0.09%. Similarly, it displayed acetylcholinesterase inhibition of 62.80 ± 0.06%. However, compound 3i showed a significantly higher inhibition percentage for protein denaturation and proteinase at 20.66 ± 0.00 and 26.42 ± 0.06%, respectively. Additionally, some in silico ADMET properties were predicted and studied. Finally, molecular docking simulation was performed inside the active site of α-amylase and acetylcholinesterase to study their interactions.

Photo fermentative biohydrogen production potential using microalgae-activated sludge co-digestion in a sequential flow batch reactor (SFBR).

Biohydrogen (bioH2) is a sustainable energy source that can produce carbon-free energy upon combustion. BioH2 can be generated from microalgae by photolytic and anaerobic digestion (AD) pathways. The AD pathway faces many challenges when scaling up using different bioreactors, particularly the continuous stirred tank reactor (CSTR) and sequential flow batch reactor (SFBR). Therefore, the performance characteristics of SFBR were analysed in this study using Chlorella vulgaris and domestic wastewater activated sludge (WWAS) co-culture. An organic loading rate (OLR) of 4.7 g COD L-1 day-1 was fed to the SFBR with a hydraulic retention time (HRT) of five days in the presence of light under anaerobic conditions. The pH of the medium was maintained at 6 using a pH controller for the incubation period of 15 days. The maximum bioH2 concentrations of 421.1 µmol L-1 and 56.6 µmol L-1 were observed in the exponential and steady-state phases, respectively. The effluent had an unusually high amount of acetate of 16.6 g L-1, which remained high with an average of 11.9 g L-1 during the steady state phase. The amount of bioH2 produced was found to be inadequate but consistent when operating the SFBR with a constant OLR. Because of the limitations in CSTR handling, operating a SFBR by optimizing OLR and HRT might be more feasible in operation for bioH2 yield in upscaling. A logistic function model was also found to be the best fit for the experimental data for the prediction of bioH2 generation using co-culture in the SFBR.

Biodesalination using halophytic cyanobacterium Phormidium keutzingianum from brackish to the hypersaline water.

The biodesalination potential at different levels of salinity of Phormidium keutzingianum (P. keutzingianum) was investigated. A wide range of salinity from brackish to hypersaline water was explored in this study to ensure the adaptability of P. keutzingianum in extreme stress conditions. Brackish to hypersaline salt solutions were tested at selected NaCl concentrations 10, 30, 50, and 70 g.L-1. Chloride, pH, nitrate, and phosphate were the main parameters measured throughout the duration of the experiment. Biomass growth estimation revealed that the studied strain is adaptable to all the salinities inoculated. During the first growth phase (till day 20), chloride ion was removed up to 43.52% and 45.69% in 10 and 30 g.L-1 of salinity, respectively. Fourier transform infrared spectrometry analysis performed on P. keutzingianum showed the presence of active functional groups at all salinity levels, which resulted in biosorption leading to the bioaccumulation process. Samples for scanning electron microscopy (SEM) analysis supported with electron dispersive X-ray spectroscopy analysis (EDS) showed NaCl on samples already on day 0. This ensures the occurrence of the biosorption process. SEM-EDS results on 10th d showed evidence of additional ions deposited on the outer surface of P. keutzingianum. Calcium, magnesium, potassium, sodium, chloride, phosphorus, and iron were indicated in SEM-EDS analysis proving the occurrence of the biomineralization process. These findings confirmed that P. keutzingianum showed biomass production, biosorption, bioaccumulation, and biomineralization in all salinities; hence, the strain affirms the biodesalination process.

A Study on the Effect of 850 nm Low-Level Diode Laser versus Electrical Stimulation in Facial Nerve Regeneration for Patients with Bell's Palsy.

INTRODUCTION: Bell's palsy is acute facial paralysis with unclear etiology that results in weakness of facial muscles or paralysis on one side of the face. METHODS: This prospective, randomized, single-blind, controlled study was conducted on 45 patients with Bell's palsy who were randomly divided into three equal groups. Two groups received either low-level laser therapy (LLLT) or electrical stimulation (E.S.) both in conjunction to medications, massage, and facial exercise treatment. The third group (control) was treated with medication, massage, and facial exercise. RESULTS: The primary outcome was the improvement of nerve conduction velocity of facial nerve while the secondary outcome was the change of Sunnybrook facial grading system (SBGS). The outcome measures were evaluated pre- and posttreatment. There was statistically significant difference between the three groups in favor of the LLLT group regarding the nerve action potential amplitude and latency, in addition to signs of nerve regeneration and improved SBGS. CONCLUSION: This short-term investigation revealed that LLLT proved to be more efficient than E.S. in facial nerve regeneration for patients with Bell's palsy.

Removal of a mixture of formaldehyde and methanol vapors in biotrickling filters under mesophilic and thermophilic conditions: Potential application in ethanol production.

Ethanol is a significant source of energy as a biofuel; however, its production using corn involves the generation of harmful emissions from both fermentation tanks and dryers. Scrubbers control the emissions from fermentation tanks, while the emissions from the dryers are controlled by regenerative thermal oxidizers. Potential alternatives to these energy- and water-intensive technologies are biotrickling filters (BTFs). In this study, two BTFs were operated in parallel to treat formaldehyde and methanol emissions in a volumetric ratio of 4:1, one at 25°C (mesophilic), and the other at 60°C (thermophilic). The mesophilic BTF simulated emissions from fermentation tanks, while the thermophilic BTF simulated emissions from dryers. Both beds were operated at an empty bed residence time of ~30 s and influent formaldehyde concentrations of 20, 50, and 100 parts per million per volume (ppmv). Formaldehyde polymerization was reduced in this study by adding NaOH to pH levels of 7.0-7.4 and heating the solution to a temperature of 60°C. BTFs have successfully removed formaldehyde at typical ethanol plants emissions ~21 ppmv. The BTF technology have the potential in replacing the conventional air treatment methods used at ethanol plants.Implications: Currently, ethanol plants remove and treat hazardous air pollutants (HAPs) using wet scrubbers from the fermenter off-gasses and using thermal oxidizers to combust off-gasses. The utilization of biotrickling filters (BTFs) for HAP removal generally and formaldehyde particularly has wide implication in the field of renewable energy. Utilizing BTFs in the 200+ ethanol plants in USA will save cost and reduce water and energy needs significantly. BTFs can reduce an ethanol plant's carbon intensity (CI) by 1 to 3 g CO2/MJ. This can result in roughly $50 million per year in additional revenue in Nebraska for instance.

An artificial neural network combined with response surface methodology approach for modelling and optimization of the electro-coagulation for cationic dye.

An artificial neural network (ANN) approach with response surface methodology (RSM) technique has been applied to model and optimize the removal process of Brilliant Green dye by batch electrocoagulation process. A multilayer perceptron (MLP) - ANN model has been trained by four input neurons which represent the reaction time, current density, pH, NaCl concentration, and two output neurons representing the dye removal efficiency (%) and electrical energy consumption (kWh/kg). The optimized hidden layer neurons were obtained based on a minimum mean squared error. The batch electrocoagulation process was optimized using central composite design with RSM once the ANN network was trained and primed to anticipate the output. At optimized condition (electrolysis time 10 min, current density 80 A/m2, initial pH 5 and electrolyte NaCl concentration 0.5 g/L), RSM projected decolorization of 98.83% and electrical energy consumption of 14.99 kWh/kg. This study shows that the removal of brilliant green dye can be successfully carried out by a batch electrocoagulation process. Therefore, the process is successfully trained by ANN and optimized by RSM for similar applications.

Identification of a promising hit from a new series of pyrazolo[1,5-a]pyrimidine based compounds as a potential anticancer agent with potent CDK1 inhibitory and pro-apoptotic properties through a multistep in vitro assessment.

A new series of sixteen new 2-arylamino-5,7-disubstituted-N-aryl-pyrazolo[1,5-a]pyrimidine-3-carboxamide derivatives was designed and synthesized. The antitumor activities of the new compounds were initially screened through the developmental therapeutics program at NCI-USA 60 cell line panel. 2-((2,4-dimethoxyphenyl)amino)-5,7-diphenylpyrazolo[1,5-a]pyrimidine-3-carboxamide (7a) was identified as a potential hit with a mean percentage of growth inhibition of 48.5% over the 60-NCI cancer cell lines whereas the other fifteen compounds ranged from 0.5 to 10.72%. In MTT assay, compound 7a exhibited IC50 of 6.28 ± 0.26 µM and 17.7 ± 0.92 µM against HCT-116 colorectal cancer and WI-38 human lung fibroblast normal cell lines, respectively. In cell cycle analysis, compound 7a arrested cell cycle at G2/M phase. It was able to inhibit CDK1 (Cyclin-Dependent Kinase 1)/Cyc B (Cyclin B) complex at IC50 161.2 ± 2.7 nM. The apoptosis-inducing ability of compound 7a was assessed through apoptosis detection flow-cytometry and gene expression analysis of apoptosis markers and caspase cascade which revealed that compound 7a exerts pro-apoptotic effect and increased expression of p53, Bax, cytochrome c, caspases (-3,-8, and-9), and decreased expression of Bcl-2. This suggests that the pro-apoptotic effect is exerted through the intrinsic pathway. The molecular docking study revealed a unique binding mode at the ATP binding pocket of CDK1/Cyc B/Cks2 through its 2,4-dimethoxyphenyl-amino. These results suggest that compound 7a could be a promising hit as a targeted protein kinase inhibitor which exerts its antitumor effect through CDK1 inhibition and pro-apoptotic action.

Unprecedented biodesalination rates-Shortcomings of electrical conductivity measurements in determining salt removal by algae and cyanobacteria.

Phormidium keutzingianum performed biodesalination of brackish water (10 g/L). The electrical conductivity (EC) was measured to evaluate the salt concentration over 80 days of cyanobacterial inoculation. Anion concentrations were measured using ion chromatography to estimate salt removal. EC-based measurements showed ∼8-10% removal efficiency in the first 20 days. However, the removal efficiency based on chloride ion concentration showed ∼40% removal in the same time frame. The pH increase was observed with growth of algal biomass. The increasing pH proposes the formation of hydroxyl and carbonate ions. Sulfuric acid was added at day 110 to neutralize them. At pH 4, the EC reduced significantly to about ∼37% confirming the chloride removal. EC should not be used to measure salt reduction as it is an obscure parameter, and therefore, EC is not the best choice to measure salinity removal using algae. Some recently published studies used only EC to estimate biodesalination, and it is anticipated that salt removal is misrepresented in those studies.

Compliance with hand sanitizer quality during the SARS-CoV-2 pandemic: Assessing the impurities in an ethanol plant.

Using alcohol-based disinfectants is an effective method for preventing the spread of COVID-19. However, non-traditional manufacturers of alcohol-based disinfectants, such as ethanol plants, need to undergo additional treatment to curb their impurities to limits set by the Food and Drug Association (FDA) to produce alcohol-based disinfectants. To transform them to disinfectant-grade alcohol, 17 process streams in a dry-mill ethanol plant were analyzed to determine the quality parameters for acetaldehyde, acetal, propanol, methanol, and water, including chemical oxygen demand, total suspended solids, and nutrients. Results suggest that the process stream generated by the distillation column requires further treatment because the acetaldehyde and acetal concentrations are significantly higher than the impurity limit set by the FDA. The addition of a second distillation column could be a potential method for addressing impurities and it will have minimal influence on hazardous air pollutant generation and water use.

Design, Synthesis, Anticancer Evaluation, Enzymatic Assays, and a Molecular Modeling Study of Novel Pyrazole-Indole Hybrids.

The molecular hybridization concept has recently emerged as a powerful approach in drug discovery. A series of novel indole derivatives linked to the pyrazole moiety were designed and developed via a molecular hybridization protocol as antitumor agents. The target compounds (5a-j and 7a-e) were prepared by the reaction of 5-aminopyrazoles (1a-e) with N-substituted isatin (4a,b) and 1H-indole-3-carbaldehyde (6), respectively. All products were characterized via several analytical and spectroscopic techniques. Compounds (5a-j and 7a-e) were screened for their cytotoxicity activities in vitro against four human cancer types [human colorectal carcinoma (HCT-116), human breast adenocarcinoma (MCF-7), human liver carcinoma (HepG2), and human lung carcinoma (A549)] using the MTT assay. The obtained results showed that the newly synthesized compounds displayed good-to-excellent antitumor activity. For example, 5-((1H-indol-3-yl)methyleneamino)-N-phenyl-3-(phenylamino)-1H-pyrazole-4-carboxamide (7a) and 5-((1H-indol-3-yl)methyleneamino)-3-(phenylamino)-N-(4-methylphenyl)-1H-pyrazole-4-carboxamide (7b) provided excellent anticancer inhibition performance against the HepG2 cancer cell line with IC50 values of 6.1 ± 1.9 and 7.9 ± 1.9 µM, respectively, compared to the standard reference drug, doxorubicin (IC50 = 24.7 ± 3.2 µM). The two powerful anticancer compounds (7a and 7b) were further subjected to cell cycle analysis and apoptosis investigation in HepG2 using flow cytometry. We have also studied the enzymatic assay of these two compounds against some enzymes, namely, caspase-3, Bcl-2, Bax, and CDK-2. Interestingly, the molecular docking study revealed that compounds 7a and 7b could well embed in the active pocket of the CDK-2 enzyme via different interactions. Overall, the prepared pyrazole-indole hybrids (7a and 7b) can be proposed as strong anticancer candidate drugs against various cancer cell lines.

Effect of exopolysaccharides produced by dairy starter cultures on biofilms formed on reverse osmosis membranes.

Two different cheese starter cultures producing exopolysaccharides (EPS+: Streptococcus thermophilus strain ST3534 and Lactococcus lactis ssp. cremoris strain JFR+) and their isogenic EPS-negative (EPS-: S. thermophilus strain ST5842 and L. lactis ssp. cremoris strain JFR-) variants were used to study the attachment of bacterial cells in the absence of growth (at 4°C) and the resultant biofilm formation on reverse osmosis membranes (at 30 or 35°C). We used M17 broth and a 10% solution of whey protein concentrate (with 35% protein) as growth media for biofilm development under static conditions. As expected, ST3534 (EPS+) showed significantly greater cell counts within biofilms than ST5842 (EPS-). In the absence of growth, however, cells of these 2 isogenic Streptococcus strains attached to the membrane in similar numbers. In contrast, JFR+ counts were significantly lower than those of JFR- under all conditions. These findings indicate that the EPS produced by S. thermophilus may play a greater role in building up the 3-dimensional structure of the biofilm, rather than only assisting during initial attachment of the cells to the membrane, whereas the EPS produced by L. lactis ssp. cremoris hampered both initial attachment to the membrane and biofilm formation. Although no differences were observed in the surface charge of the cells between the 2 EPS-producing cultures, surface hydrophobicity was associated with the different adhesive properties of these microorganisms. In conclusion, our results exclude the hypothesis that all EPS-producing starter cultures have an advantage in regard to their ability to form biofilm on membrane separation surfaces. In contrast, variations between different EPS, with hydrophobicity being an important influencing feature, modify adhesive behavior to reverse osmosis membranes.