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Organic/silicon hybrid solar cells have attracted much interest due to their cheap fabrication process and simple device structure. A category of organic substances, Dibenzothiophene–Spirobifluorene–Dithiophene (DBBT-mTPA-DBT), comprises dibenzo [d,b] thiophene and 3-(3-methoxyphenyl)-6-(4-methoxyphenyl)-9H-Carbazole, which function as electron donors. In contrast, methanone is an electron acceptor, with an ∆Est of 3.19 eV. This work focused on hybrid solar cells based on the guest–host phenomena of DBBT-mTPA-DBT and CBP. Using a Si/poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) hybrid solar cell with an ultra-thin Dibenzothiophene–Spirobifluorene–Dithienothiophene (DBBT-mTPA-DBT) interlayer between Si and Al led to a PCE of 17.5 ± 2.5%. The DBBT-mTPA-DBT interlayer substantially improved the Si/Al interface, reducing contact resistance from 6.5 × 10⁻1 Ω·cm2 to 3.5 × 10⁻2 Ω·cm2. This improvement increases electron transport efficiency from silicon to aluminum and reduces carrier recombination. The solar cell containing the DBBT-mTPA-DBT/Al double-layer cathode shows a 10.85% increase in power conversion efficiency relative to the standard Al cathode device.

This review is dedicated to sustainable practices in liquid chromatography. HPLC and UHPLC methods contribute significantly to routine analytical techniques. Therefore, the transfer of classical liquid chromatographic methods into sustainable ones is of utmost importance in moving toward sustainable development goals. Among other principles to render a liquid chromatographic method green, the substitution of the organic solvent component in the mobile phase with a greener one received great attention. This review concentrates on choosing the best alternative green organic solvent to replace the classical solvent in the mobile phase for easy, rapid transfer to a more sustainable normal phase or reversed-phase liquid chromatography. The main focus of this review will be on describing the transfer of non-green to green and white chromatographic methods in an effort to elevate sustainability best practices in analytical chemistry. The greenness properties and greenness ranking, in addition to the chromatographic suitability of seventeen organic solvents for liquid chromatography, are mentioned to have a clear insight into the issue of rapidly choosing the appropriate solvent to transfer a classical HPLC or UHPLC method into a more sustainable one. A simple guide is proposed for making the liquid chromatographic method more sustainable.

Nanoemulsions are gaining interest in a variety of products as a means of integrating easily degradable bioactive compounds, preserving them from oxidation, and increasing their bioavailability. However, preparing stable emulsion compositions with the desired characteristics is a difficult task. The aim of this study was to encapsulate the Tinospora cordifolia aqueous extract (TCAE) into a water in oil (W/O) nanoemulsion and identify its critical process and formulation variables, like oil (27–29.4 mL), the surfactant concentration (0.6–3 mL), and sonication amplitude (40% to 100%), using response surface methodology (RSM). The responses of this formulation were studied with an analysis of the particle size (PS), free fatty acids (FFAs), and encapsulation efficiency (EE). In between, we have studied a fishbone diagram that was used to measure risk and preliminary research. The optimized condition for the formation of a stable nanoemulsion using quality by design was surfactant (2.43 mL), oil concentration (27.61 mL), and sonication amplitude (88.6%), providing a PS of 171.62 nm, FFA content of 0.86 meq/kg oil and viscosity of 0.597 Pa.s for the blank sample compared to the enriched TCAE nanoemulsion with a PS of 243.60 nm, FFA content of 0.27 meq/kg oil and viscosity of 0.22 Pa.s. The EE increases with increasing concentrations of TCAE, from 56.88% to 85.45%. The RSM response demonstrated that both composition variables had a considerable impact on the properties of the W/O nanoemulsion. Furthermore, after the storage time, the enriched TCAE nanoemulsion showed better stability over the blank nanoemulsion, specially the FFAs, and the blank increased from 0.142 to 1.22 meq/kg oil, while TCAE showed 0.266 to 0.82 meq/kg.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as “sandalwood oils”. Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-β-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the β-isomer.

Organic/silicon hybrid solar cells have attracted much interest due to their cheap fabrication process and simple device structure. A category of organic substances, Dibenzothiophene–Spirobifluorene–Dithiophene (DBBT-mTPA-DBT), comprises dibenzo [d,b] thiophene and 3-(3-methoxyphenyl)-6-(4-methoxyphenyl)-9H-Carbazole, which function as electron donors. In contrast, methanone is an electron acceptor, with an ∆Est of 3.19 eV. This work focused on hybrid solar cells based on the guest–host phenomena of DBBT-mTPA-DBT and CBP. Using a Si/poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT: PSS) hybrid solar cell with an ultra-thin Dibenzothiophene–Spirobifluorene–Dithienothiophene (DBBT-mTPA-DBT) interlayer between Si and Al led to a PCE of 17.5 ± 2.5%. The DBBT-mTPA-DBT interlayer substantially improved the Si/Al interface, reducing contact resistance from 6.5 × 10⁻1 Ω·cm2 to 3.5 × 10⁻2 Ω·cm2. This improvement increases electron transport efficiency from silicon to aluminum and reduces carrier recombination. The solar cell containing the DBBT-mTPA-DBT/Al double-layer cathode shows a 10.85% increase in power conversion efficiency relative to the standard Al cathode device. [ABSTRACT FROM AUTHOR]

The plant Carpobrotus edulis has traditionally been known for its wide applications in diseases, especially vitiligo, which is characterized by patches and white macules caused by the loss of melanocytes. One of the chemical treatments for vitiligo consists mainly of skin repigmentation and usually leads to a non-durable effect by inhibiting the Janus kinase (JAK) signal transduction (STAT pathway). JAK inhibitors generally block multiple JAK tyrosine kinases, which leads to secondary effects. In this study, natural molecules from Carpobrotus edulis were extracted and tested using a structure-based drug-design approach and pharmacophore modeling. The best-fit candidate from the extracted molecules was compared to the chemical molecules used. The results indicated a similarity between the chemical and natural ligands which suggested the potential use of the natural product against vitiligo. The main finding of this research work was the discovery of a new molecule extracted from a natural plant and the detection of its anti-vitiligo activity using an in-silico approach. This method can significantly reduce the cost of searching for potential medicinal molecules.

Eucalyptus, a therapeutic plant mentioned in the ancient Algerian pharmacopeia, specifically two species belonging to the Myrtaceae family, E. radiata and E. cinerea, were investigated in this study for their antibacterial, antioxidant, and anti-inflammatory properties. The study used aqueous extracts (AE) obtained from these plants, and the extraction yields were found to be different. The in vitro antibacterial activity was evaluated using a disc diffusion assay against three typical bacterial strains. The results showed that the two extracts were effective against all three strains. Both extracts displayed significant antioxidant activity compared to BHT. The anti-inflammatory impact was evaluated using a protein (BSA) inhibition denaturation test. The E. radiata extract was found to inhibit inflammation by 85% at a concentration of 250 µg/mL, significantly higher than the Aspirin. All phytoconstituents present good pharmacokinetic characteristics without toxicity except very slight toxicity of terpineol and cineol and a maximum binding energy of −7.53 kcal/mol for its anti-TyrRS activity in silico. The study suggests that the extracts and their primary phytochemicals could enhance the efficacy of antibiotics, antioxidants, and non-steroidal anti-inflammatory drugs (NSAIDs). As pharmaceutical engineering experts, we believe this research contributes to developing natural-based drugs with potential therapeutic benefits.

In eukaryotic cells, membrane proteins play a crucial role. They fall into three categories: intrinsic proteins, extrinsic proteins, and proteins that are essential to the human genome (30% of which is devoted to encoding them). Hydrophobic interactions inside the membrane serve to stabilize integral proteins, which span the lipid bilayer. This review investigates a number of computational and experimental methods used to study membrane proteins. It encompasses a variety of technologies, including electrophoresis, X-ray crystallography, cryogenic electron microscopy (cryo-EM), nuclear magnetic resonance spectroscopy (NMR), biophysical methods, computational methods, and artificial intelligence. The link between structure and function of membrane proteins has been better understood thanks to these approaches, which also hold great promise for future study in the field. The significance of fusing artificial intelligence with experimental data to improve our comprehension of membrane protein biology is also covered in this paper. This effort aims to shed light on the complexity of membrane protein biology by investigating a variety of experimental and computational methods. Overall, the goal of this review is to emphasize how crucial it is to understand the functions of membrane proteins in eukaryotic cells. It gives a general review of the numerous methods used to look into these crucial elements and highlights the demand for multidisciplinary approaches to advance our understanding.

Peppers are among the spices possessing a wide plethora of biological properties due to their excellent supply of health-related metabolites. Capsicum annuum L. (Solanaceae) is cultivated throughout Tunisia, and there is a shortage of information on the identification of the secondary metabolites in the seeds of this species as well as on their biological activities. In the present work, we intended to undertake a chemical characterization of the bioactive compounds from the hydro-methanolic seed extract of C. annuum as well as an evaluation of its broad spectrum of antimicrobial and antioxidant activities. The chemical profile was evaluated by RP-HPLC-DAD-QTOF-MS/MS, whereas the total phenol and flavonoid content, antioxidant, and antimicrobial activities were determined in in vitro assays. In this work, 45 compounds belonging to various phytochemical classes, such as organic acids (2), phenolic compounds (4 phenolic acids and 5 flavonoids), capsaicinoids (3), capsianosides (5), fatty acids (13), amino acids (1), sphingolipids (10), and steroids (2) were identified in the hydro-methanolic seed extract of C. annuum. The phenolic and flavonoid content (193.7 mg GAE/g DW and 25.1 mg QE/g DW, respectively) of the C. annuum extract correlated with the high antiradical activity (IC50 = 45.0 µg/mL), reducing power (EC50 = 61.3 µg/mL) and chelating power (IC50 = 79.0 µg/mL) activities. The hydro-methanolic seed extract showed an important antimicrobial activity against seven bacterial and four fungal strains. In fact, the inhibition zones (IZs) for bacteria ranged from 9.00 ± 1.00 mm to 12.00 ± 0.00 mm; for fungi, the IZs ranged from 12.66 ± 0.57 mm to 13.66 ± 0.57 mm. The minimal inhibition concentration and minimal bactericidal concentration values showed that the extract was more effective against fungi than bacteria.

To address the high tolerance of biofilms to antibiotics, it is urgent to develop new strategies to fight against these bacterial consortia. An innovative antibiofilm nanovector drug delivery system, consisting of Dispersin B-permethylated-β-cyclodextrin/ciprofloxacin adamantyl (DspB-β-CD/CIP-Ad), is described here. For this purpose, complexation assays between CIP-Ad and (i) unmodified β-CD and (ii) different derivatives of β-CD, which are 2,3-O-dimethyl-β-CD, 2,6-O-dimethyl-β-CD, and 2,3,6-O-trimethyl-β-CD, were tested. A stoichiometry of 1/1 was obtained for the β-CD/CIP-Ad complex by NMR analysis. Isothermal Titration Calorimetry (ITC) experiments were carried out to determine Ka, ΔH, and ΔS thermodynamic parameters of the complex between β-CD and its different derivatives in the presence of CIP-Ad. A stoichiometry of 1/1 for β-CD/CIP-Ad complexes was confirmed with variable affinity according to the type of methylation. A phase solubility study showed increased CIP-Ad solubility with CD concentration, pointing out complex formation. The evaluation of the antibacterial activity of CIP-Ad and the 2,3-O-dimethyl-β-CD/CIP-Ad or 2,3,6-O-trimethyl-β-CD/CIP-Ad complexes was performed on Staphylococcus epidermidis (S. epidermidis) strains. The Minimum Inhibitory Concentration (MIC) studies showed that the complex of CIP-Ad and 2,3-O-dimethyl-β-CD exhibited a similar antimicrobial activity to CIP-Ad alone, while the interaction with 2,3,6-O-trimethyl-β-CD increased MIC values. Antimicrobial assays on S. epidermidis biofilms demonstrated that the synergistic effect observed with the DspB/CIP association was partly maintained with the 2,3-O-dimethyl-β-CDs/CIP-Ad complex. To obtain this “all-in-one” drug delivery system, able to destroy the biofilm matrix and release the antibiotic simultaneously, we covalently grafted DspB on three carboxylic permethylated CD derivatives with different-length spacer arms. The strategy was validated by demonstrating that a DspB-permethylated-β-CD/ciprofloxacin-Ad system exhibited efficient antibiofilm activity.

Plaque psoriasis is a common, long-lasting illness that affects the immune system and causes significant negative impacts on a patient’s physical health, well-being, and ability to work effectively. Deucravacitinib (DEU) is the first oral medication used in the treatment of plaque psoriasis, a chronic skin condition that causes red, scaly patches on the skin. DEU is a type of medication called an oral Janus kinase (JAK) inhibitor, which works by blocking specific enzymes that play a role in the inflammation and immune response associated with psoriasis. Therefore, a quick, easy, novel, reliable, sensitive, and straightforward liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to analyze DEU in plasma samples. The LC-MS/MS method for the determination of DEU in human plasma was based on using trimethoprim as an internal standard (IS). The separation of DEU and IS was carried out via liquid–liquid extraction (LLE). The extract was then subjected to the chromatographic system separation using the ACE-C18 column (4.6 × 100 mm, 5 µm). The mobile phase employed consisted of methanol and a solution of 2 mM ammonium formate (80:20 v/v, respectively). The flow rate used was set at 0.9 mL min−1. The creative strategy was performed by running an ABSCIEX API 4000 mass spectrometer with an electron spray ionization source in multiple reaction monitoring (MRM) mode. The ion transitions m/z 426.3 → 358.2 were used for DEU quantitation, while the ion transitions m/z 291.1 → 261.1 were used for trimethoprim quantitation. The accuracy, precision, linearity, recovery, and selectivity of DEU were deemed acceptable when validated for a concentration range between 0.500 and 601.050 ng/mL, utilizing a weighting factor of 1/x2.

The ongoing COVID-19 pandemic has resulted in a global panic because of its continual evolution and recurring spikes. This serious malignancy is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak, millions of people have been affected from December 2019 till now, which has led to a great surge in finding treatments. Despite trying to handle the pandemic with the repurposing of some drugs, such as chloroquine, hydroxychloroquine, remdesivir, lopinavir, ivermectin, etc., against COVID-19, the SARS-CoV-2 virus continues its out-of-control spread. There is a dire need to identify a new regimen of natural products to combat the deadly viral disease. This article deals with the literature reports to date of natural products showing inhibitory activity towards SARS-CoV-2 through different approaches, such as in vivo, in vitro, and in silico studies. Natural compounds targeting the proteins of SARS-CoV-2—the main protease (Mpro), papain-like protease (PLpro), spike proteins, RNA-dependent RNA polymerase (RdRp), endoribonuclease, exoribonuclease, helicase, nucleocapsid, methyltransferase, adeno diphosphate (ADP) phosphatase, other nonstructural proteins, and envelope proteins—were extracted mainly from plants, and some were isolated from bacteria, algae, fungi, and a few marine organisms.

Many literature reports revealed the anticancer activity of pyridine and thiazole derivatives, especially in lung cancer. Therefore, a new series of thiazolyl pyridines linked with thiophene moiety via hydrazone group was prepared by one-pot multi-component reaction of (E)-1-(4-methyl-2-(2-(1-(thiophen-2-yl)ethylidene)hydrazinyl)thiazol-5-yl)ethanone with benzaldehyde derivatives and malononitrile in a good yield. Then, compound 5 and the thiazolyl pyridines were investigated for their in vitro anticancer activity against lung cancer (A549) cell line using MTT assay compared to doxorubicin as a reference drug. The structure of all the newly synthesized compounds was established based on spectroscopic data and elemental analyses. For better insight to investigate their mechanism of action on A549 cell line, docking studies were performed, targeting epidermal growth factor receptor (EGFR) tyrosine kinase. The results obtained revealed that the tested compounds displayed excellent anticancer activities against lung cancer cell line except 8c and 8f compared to reference drug. Based on the data obtained, it can be inferred that the novel compounds, as well as their key intermediate, compound 5, demonstrated potent anticancer activity against lung carcinoma by inhibiting EGFR.

This study aimed to improve the physical, mechanical, and biological properties of a monolayer pectin (P) film containing nanoemulsified trans-Cinnamaldehyde (TC) by incorporating it between inner and outer layers of ethylcellulose (EC). The nanoemulsion had an average size of 103.93 nm and a zeta potential of −46 mV. The addition of the nanoemulsion increased the opacity of the film, reduced its moisture absorption capacity, and improved its antimicrobial activity. However, the tensile strength and elongation at break of the pectin films decreased after the incorporation of nanoemulsions. Multilayer films (EC/P/EC) showed a higher resistance to breaking and better extensibility compared to monolayer films. The antimicrobial activity of both mono and multilayer films was effective in inhibiting the growth of foodborne bacteria during storage of ground beef patties at 8 °C for 10 days. This study suggests that biodegradable antimicrobial multilayer packaging films can be effectively designed and applied in the food packaging industry.

The continuous search for novel biobased polymers with high-performance properties has highlighted the role of monofuranic-based polyesters as some of the most promising for future plastic industry but has neglected the huge potential for the polymers’ innovation, relatively low cost, and synthesis easiness of 5,5′-isopropylidene bis-(ethyl 2-furoate) (DEbF), obtained from the platform chemical, worldwide-produced furfural. In this vein, poly(1,12-dodecylene 5,5′-isopropylidene -bis(ethyl 2-furoate)) (PDDbF) was introduced, for the first time, as a biobased bisfuranic long-chain aliphatic polyester with an extreme flexibility function, competing with fossil-based polyethylene. This new polyester in-depth characterization confirmed its expected structure (FTIR, 1H, and 13C NMR) and relevant thermal features (DSC, TGA, and DMTA), notably, an essentially amorphous character with a glass transition temperature of −6 °C and main maximum decomposition temperature of 340 °C. Furthermore, PDDbF displayed an elongation at break as high as 732%, around five times higher than that of the 2,5-furandicarboxylic acid counterpart, stressing the unique features of the bisfuranic class of polymers compared to monofuranic ones. The enhanced ductility combined with the relevant thermal properties makes PDDbF a highly promising material for flexible packaging.

A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1H-1,2,4-triazoles, aromatic aldehydes and ethyl acetoacetate. The compound structures were confirmed by IR, 1H-NMR, 13C-NMR, HRMS and X-ray analyses. The biological activity of these compounds as antitumor agents was evaluated. Their antitumor activities against cancer cell lines (MDA-MB-231 and MCF-7) were tested by the MTT in vitro method. Among them, compounds 4c and 4j displayed the best antitumor activity with IC50 values of 17.83 μM and 19.73 μM against MDA-MB-231 and MCF-7 cell lines, respectively, compared to the Cisplatin reference.

Chronic lymphocytic leukemia (CLL) is an incurable neoplasm of B-lymphocytes, which accounts for about one-third of all leukemias. Ocimum sanctum, an herbaceous perennial, is considered as one of the important sources of drugs for the treatment of various diseases, including cancers and autoimmune diseases. The present study was designed to screen various phytochemicals of O. sanctum for discovering their potential to inhibit Bruton’s tyrosine kinase (BTK), a well-known drug target of CLL. Various phytochemicals of O. sanctum were screened for their potential to inhibit BTK using several in silico protocols. First, the molecular docking approach was used to calculate the docking scores of the selected phytochemicals. Then, the selected top-ranked phytochemicals were screened for their physicochemical characteristics using ADME analysis. Finally, the stability of the selected compounds in their corresponding docking complexes with BTK was analysed using molecular dynamics simulations. Primarily, our observations revealed that, out of the 46 phytochemicals of O. sanctum, six compounds possessed significantly better docking scores (ranging from −9.2 kcal/mol to −10 kcal/mol). Their docking scores were comparable to those of the control inhibitors, acalabrutinib (−10.3 kcal/mol), and ibrutinib (−11.3 kcal/mol). However, after ADME analysis of these top-ranked six compounds, only three compounds (Molludistin, Rosmarinic acid, and Vitexin) possessed drug likeliness characteristics. During the MD analysis, the three compounds Molludistin, Rosmarinic acid, and Vitexin were found to remain stable in the binding pocket in their corresponding docking complexes with BTK. Therefore, among the 46 phytochemicals of O. sanctum tested in this study, the three compounds, Molludistin, Rosmarinic acid, and Vitexin are the best inhibitors of BTK. However, these findings need to be confirmed by biological experiments in the laboratory.

Molecular docking is a key method used in virtual screening (VS) campaigns to identify small-molecule ligands for drug discovery targets. While docking provides a tangible way to understand and predict the protein-ligand complex formation, the docking algorithms are often unable to separate active ligands from inactive molecules in practical VS usage. Here, a novel docking and shape-focused pharmacophore VS protocol is demonstrated for facilitating effective hit discovery using retinoic acid receptor-related orphan receptor gamma t (RORγt) as a case study. RORγt is a prospective target for treating inflammatory diseases such as psoriasis and multiple sclerosis. First, a commercial molecular database was flexibly docked. Second, the alternative docking poses were rescored against the shape/electrostatic potential of negative image-based (NIB) models that mirror the target’s binding cavity. The compositions of the NIB models were optimized via iterative trimming and benchmarking using a greedy search-driven algorithm or brute force NIB optimization. Third, a pharmacophore point-based filtering was performed to focus the hit identification on the known RORγt activity hotspots. Fourth, free energy binding affinity evaluation was performed on the remaining molecules. Finally, twenty-eight compounds were selected for in vitro testing and eight compounds were determined to be low μM range RORγt inhibitors, thereby showing that the introduced VS protocol generated an effective hit rate of ~29%.

This review is dedicated to sustainable practices in liquid chromatography. HPLC and UHPLC methods contribute significantly to routine analytical techniques. Therefore, the transfer of classical liquid chromatographic methods into sustainable ones is of utmost importance in moving toward sustainable development goals. Among other principles to render a liquid chromatographic method green, the substitution of the organic solvent component in the mobile phase with a greener one received great attention. This review concentrates on choosing the best alternative green organic solvent to replace the classical solvent in the mobile phase for easy, rapid transfer to a more sustainable normal phase or reversed-phase liquid chromatography. The main focus of this review will be on describing the transfer of non-green to green and white chromatographic methods in an effort to elevate sustainability best practices in analytical chemistry. The greenness properties and greenness ranking, in addition to the chromatographic suitability of seventeen organic solvents for liquid chromatography, are mentioned to have a clear insight into the issue of rapidly choosing the appropriate solvent to transfer a classical HPLC or UHPLC method into a more sustainable one. A simple guide is proposed for making the liquid chromatographic method more sustainable. [ABSTRACT FROM AUTHOR]

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as 1H-NMR, 13C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01–SM-IMP-13 series have HOMO/LUMO gaps within 4.43–4.69 eV, whereas the compounds of the DA-01–DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24–4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities.

In East Africa, Dodonaea angustifolia (L.f.) is a well-known medicinal herb. Its leaf is primarily studied in light of its ethnobotanical use. In terms of phytochemistry and biological activity, its flower is not studied. In a prior study, our team looked into phytochemical screening, antioxidant activity, and total phenolic levels. This study aims to compare the profiles and biological activities of the leaf and flower samples of D. angustifolia and to present therapeutic alternatives. The leaf and flower sample powders were extracted with methanol using ultrasound-assisted extraction (UAE). HPTLC profile was obtained using CAMAG—HPTLC equipped with VisionCATS software. Antimicrobial agar well diffusion assay and minimum inhibition concentration (MIC) were determined. The leaf and flower extracts of D. angustifolia showed antibacterial activity with a MIC value of 20 µg/mL against Enterococcus faecalis and Listeria monocytogenes. Similarly, 40 µg/mL was found to be effective against Aspergillus flavus. D. angustifolia flower is a rich source of flavonoids and phenolic acids. Because of its antibacterial properties and profile, which are almost the same, the flower is emerging as a viable option for medicinal alternatives.

Four eco-friendly, cost-effective, and fast stability-indicating UV-VIS spectrophotometric methods were validated for cefotaxime sodium (CFX) determination either in the presence of its acidic or alkaline degradation products. The applied methods used multivariate chemometry, namely, classical least square (CLS), principal component regression (PCR), partial least square (PLS), and genetic algorithm-partial least square (GA-PLS), to resolve the analytes’ spectral overlap. The spectral zone for the studied mixtures was within the range from 220 to 320 nm at a 1 nm interval. The selected region showed severe overlap in the UV spectra of cefotaxime sodium and its acidic or alkaline degradation products. Seventeen mixtures were used for the models’ construction, and eight were used as an external validation set. For the PLS and GA-PLS models, a number of latent factors were determined as a pre-step before the modelsʹ construction and found to be three for the (CFX/acidic degradants) mixture and two for the (CFX/alkaline degradants) mixture. For GA-PLS, spectral points were minimized to around 45% of the PLS models. The root mean square errors of prediction were found to be (0.19, 0.29, 0.47, and 0.20) for the (CFX/acidic degradants) mixture and (0.21, 0.21, 0.21, and 0.22) for the (CFX/alkaline degradants) mixture for CLS, PCR, PLS, and GA-PLS, respectively, indicating the excellent accuracy and precision of the developed models. The linear concentration range was studied within 12–20 μg mL–1 for CFX in both mixtures. The validity of the developed models was also judged using other different calculated tools such as root mean square error of cross validation, percentage recoveries, standard deviations, and correlation coefficients, which indicated excellent results. The developed methods were also applied to the determination of cefotaxime sodium in marketed vials, with satisfactory results. The results were statistically compared to the reported method, revealing no significant differences. Furthermore, the greenness profiles of the proposed methods were assessed using the GAPI and AGREE metrics.

Numerous food organizations have identified excessive calorie consumption and accompanying ailments as significant health risks associated with high sugar consumption. Administering stevioside (ST), sucralose (SU), and the two synergically (SU+ST) affected normal rats’ weight gain. In the current study, SU showed the highest undesired effect. Indeed, administering the three treatments to diabetic rats (DR) did not improve the rats’ weight gain. Although, insulin injection synergically with the treatments improved the weight gain, as recorded after three weeks. The best-improving rate was observed in the ST group. After the administration of ST and ST+SU to the DR, the blood glucose level (GL) was positively affected, with SU having no effects on reducing the GL. A considerable reduction in serum insulin (SIL) was noted in the DR+SU group. On the contrary, ST did not negatively affect the SIL, rather an improvement was recorded. In addition, giving SU did not significantly affect the ALT level in the DR or normal rats (NR). A significant improvement in total bilirubin (TBILI) was observed when insulin was injected with ST or SU in DR groups. Further, triglycerides (TG) after administering ST, SU, or ST+SU to NR had no significant difference compared to the control group (NR). Although, the three treatments markedly but not significantly lowered TG in the DR. For total cholesterol (CHO), both DR and NR had no significant effect after the three treatments. No histopathological alterations were recorded in the NR group. Diffuse and severe atrophy of the islands of Langerhans due to depletion of their cells and mild papillary hyperplasia of the pancreatic ducts were represented by a slightly folded ductal basement membrane and newly formed ductules in STZ-DR. Simultaneous atrophy and absence of the cells of islands of Langerhans besides ductal hyperplasia were evident in DR+SU. Hyperplastic ductal epithelium and atrophic Langerhans cells were seen in DR+SU+In. Degeneration and mild atrophy were observed in the islands of Langerhans structures. There was essentially no noticeable change after utilizing ST. A slight shrinkage of the Langerhans’ islets was detected in DR+ST. In DR+ST+In, no histopathological alterations in the islands of Langerhans were recorded. Congestion in the stromal blood vessels associated with degenerative and necrotic changes in the cells of the islands of Langerhans in DR+SU+ST was observed. In NR+SU, congestion of the blood vessels associated with mild atrophy in the islands of Langerhans and dilatation in stromal blood vessels was noticed. In conclusion, ST is safe, and SU should be taken cautiously, such as mixing with ST and/or taken at a very low concentration to avoid its drastic effect on the human body.

Shigellosis is one of the major causes of death in children worldwide. Flavonoids and phenolic acids are expected to demonstrate anti-shigellosis activity and anti-diarrheal properties. The aerial part of A. integrifolia is commonly used against diarrhea. This study aimed to identify flavonoids and phenolic acids responsible for this therapeutic purpose. Antioxidant activity, total phenol content, and total flavonoid content were determined. The antibacterial activity of the aerial part against Shigella spp. was also tested using the agar well diffusion method. HPLC analysis was performed using UHPLC-DAD for different extracts of the aerial part. Autodock Vina in the PyRx platform was used to screen responsible components. Ciprofloxacin was used as a reference drug. An enzyme taking part in pyrimidine biosynthesis was used as a target protein. Molecular docking results were visualized using Discovery Studio and LigPlot1.4.5 software. Antioxidant activity, total phenol content, and total flavonoid content are more significant for the aerial part of A. integrifolia. From HPLC analysis, the presence of the flavonoids, quercetin, myricetin, and rutin and the phenolic acids gallic acid, chlorogenic acid, and syringic acid were identified from the aerial part of A. integrifolia. Regarding the antibacterial activity, the aerial part shows considerable activity against Shigella spp. Binding energies, RMSD and Ki values, interaction type, and distance are considered to identify the components most likely responsible for the therapeutic effects and observed activity. Antioxidant activity, total phenol content, and total flavonoid content of the aerial part are in line with anti-shigellosis activity. The top five components that are most likely potentially responsible for therapeutic purposes and anti-shigellosis activity are chlorogenic acid, rutin, dihydroquercetin, dihydromyricetin, and kaempferol.

The analytical quality by design (AQbD) approach is utilized for developing and validating the simple, sensitive, cost-effective reverse-phase high performance liquid chromatographic method for the estimation of xanthohumol (XH) in bulk and nanoformulations. The Box–Behnken design (BBD) is applied for method optimization. The mobile phase ratio, pH and flow rate were selected as independent variables, whereas retention time, peak area, peak height, tailing factor, and theoretical plates were selected as dependent variables. The chromatogram of XH obtained under optimized conditions has given optimum conditions such as retention time (5.392 min), peak area (1,226,737 mAU), peak height (90,121 AU), tailing factor (0.991) and theoretical plates (4446.667), which are contoured in the predicted values shown by BBD. Validation of the method has been performed according to ICH Q2(R1) recommendations, using optimized conditions for linearity, limit of detection (LOD) and limit of quantification (LOQ), accuracy, precision, robustness and system suitability. All the values of validation parameters lie within the acceptable limits prescribed by ICH. Therefore, the developed and validated method of XH by the AQbD approach can be applied for the estimation of XH in bulk and various nanoformulations.

In our continuous study for some African plants as a source for antitrypanosomally and cytotoxic active drugs, nine different plants belonging to the Crassulaceae family have been selected for the present study. Sedum sieboldii leaves extract showed an antitrypanosomal activity against Trypanosoma brucei with an IC50 value of 8.5 µg/mL. In addition, they have cytotoxic activities against (HCT-116), (HEPG-2) and (MCF-7), with IC50 values of 28.18 ± 0.24, 22.05 ± 0.66, and 26.47 ± 0.85 µg/mL, respectively. Furthermore, the extract displayed inhibition against Topoisomerase-1 with an IC50 value of 1.31 µg/mL. It showed the highest phenolics and flavonoids content among the other plants’ extracts. In order to identify the secondary metabolites which may be responsible for such activities, profiling of the polar secondary metabolites of S. sieboldii extract via Ultra-Performance Liquid Chromatography coupled to High-Resolution QTOF-MS operated in negative and positive ionization modes, which revealed the presence of 46 metabolites, including flavonoids, phenolic acids, anthocyanidins, coumarin, and other metabolites.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski’s rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization.

The novel Aerva javanica absorbent was applied for the removal of thirteen selected metal ions from a distilled water solution of each metal by the batch adsorption method. The optimization remediation parameters of the metal ions for the batch adsorption approach were developed, which were the initial concentrations (60 ppm), contact time (60 min) and pH (7). The basic properties of metal ion affected the adsorption results; therefore, 21 properties of metal ions were selected, which are called “descriptors”. The most significant descriptors were selected that were vital for the adsorption results, such as covalent index, polarizability and ion charge. The developed model equation by the descriptors provided more than 80% accuracy in the predicted results. Furthermore, Freundlich and Langmuir adsorption models were also applied on the results. Constants of the Freundlich and Langmuir models were also used for model generation, and the results revealed the importance of a covalent index for the removal phenomenon of metal ions. The current study provided a suitable Ion Character Property Relationship (IC-PR) for the removal of metal ions, and future predictions can be achieved on the proposed adsorbent with significant accuracy. The ecofriendly and cost effective Aerva javanica absorbent in the batch experimental model of the current study predicted that this novel absorbent can be used for the removal of a wide spectrum of heavy metal ions from different sources of waste waters.

Micellar-enhanced ultrafiltration (MEUF), being a separation technique, was used to remove cobalt metal ion (Co2+) from their aqueous solutions in an application to reduce the toxicity level from industrial effluents using a micellar solution of anionic and cationic surfactants. The metal ions were first adsorbed by using anionic surfactants, i.e., sodium dodecyl sulfate (SDS) and sodium oleate (SO). The calculations for partition (Kx) and binding constants (Kb) and their respective free energy of partition and binding (ΔGp and ΔGb kJmol−1) helped significantly to find out the extent of binding or interaction of Co2+ with the surfactant and ΔGp and ΔGb were found to be −29.50 and −19.38 kJmol−1 for SDS and −23.95 and −12.67 kJmol−1 in the case of SO. MEUF work was also performed to find out the optimal conditions to remove metal pollutants from the aqueous system. For the said purpose, various factors and concentrations effect were studied, such as the concentration of the surfactant, concentration of the electrolyte (NaCl), transmembrane pressure, RPM, and pH. The efficiency of this process was checked by calculating various parameters, such as rejection percentage (R%) and permeate flux (J). A maximum rejection of 99.95% with SDS and 99.99% with SO was attained.

Ten new differently substituted 3-benzyl-5-aryl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidin-4,6,11-triones 3 were synthesized by a simple and cost-efficient procedure in a one-pot, three-component reaction from readily available ethyl 2-amino-4-aryl-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-3-carboxylates, benzylamine and triethyl orthoformate under solvent- and catalyst-free conditions. All the new compounds were screened for their antiproliferative activity against two colorectal-cancer-cell lines. The results showed that the compounds 3-benzyl-5-phenyl-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3a) and 3-benzyl-5-(3-hydroxyphenyl)-3,5-dihydro-4H-benzo[6,7]chromeno[2,3-d]pyrimidine-4,6,11-trione (3g) exhibited the most potent balanced inhibitory activity against human LoVo and HCT-116 cancer cells.

Neurodegenerative diseases exert an overwhelming socioeconomic burden all around the globe. They are mainly characterized by modified protein accumulation that might trigger various biological responses, including oxidative stress, inflammation, regulation of signaling pathways, and excitotoxicity. These disorders have been widely studied during the last decade in the hopes of developing symptom-oriented therapeutics. However, no definitive cure has yet been discovered. Tea is one of the world’s most popular beverages. The same plant, Camellia Sinensis (L.).O. Kuntze, is used to make green, black, and oolong teas. Green tea has been most thoroughly studied because of its anti-cancer, anti-obesity, antidiabetic, anti-inflammatory, and neuroprotective properties. The beneficial effect of consumption of tea on neurodegenerative disorders has been reported in several human interventional and observational studies. The polyphenolic compounds found in green tea, known as catechins, have been demonstrated to have many therapeutic effects. They can help in preventing and, somehow, treating neurodegenerative diseases. Catechins show anti-inflammatory as well as antioxidant effects via blocking cytokines’ excessive production and inflammatory pathways, as well as chelating metal ions and free radical scavenging. They may inhibit tau protein phosphorylation, amyloid beta aggregation, and release of apoptotic proteins. They can also lower alpha-synuclein levels and boost dopamine levels. All these factors have the potential to affect neurodegenerative disorders. This review will examine catechins’ neuroprotective effects by highlighting their biological, pharmacological, antioxidant, and metal chelation abilities, with a focus on their ability to activate diverse cellular pathways in the brain. This review also points out the mechanisms of catechins in various neurodegenerative and cognitive diseases, including Alzheimer’s, Parkinson’s, multiple sclerosis, and cognitive deficit.

Background: Europinidin is a derivative of delphinidin obtained from the plants Plumbago Europea and Ceratostigma plumbaginoides. This herb has wide medicinal applications in treating various diseases but there are very few studies available on this bioactive compound. Considering this background, the present study is designed for the evaluation of Europinidin against Parkinson’s disease. Aim: The investigation aims to assess the effect of Europinidin in the rotenone-activated Parkinson’s paradigm. Methods: To evaluate neuroprotective activity, rotenone (1.5 mg/kg s.c) and europinidin (10 mg/kg and 20 mg/kg) was administered in rats for 21 days. The behavioural parameters were performed before sacrificing the rats. On the 22nd day, all the rats were assessed for biochemical markers (SOD, GSH, MDA, Catalase), neurotransmitter levels (Dopamine, 5-HIAA, DOPAC, and HVA levels), and neuroinflammatory markers (IL-6, IL-1β and TNF-α). Results: It was found that rotenone produced significant (p < 0.001) oxidative damage, a cholinergic deficit, dopaminergic loss, and a rise in neuroinflammatory markers in rats. Conclusion: The study concludes that europinidin possesses anti-oxidant and anti-inflammatory properties. The results suggest the therapeutic role of europinidin against rotenone-activated behavioural, biochemical, and neuroinflammatory alterations in rats.

Xanthohumol (XH) a prenylated chalcone has diverse therapeutic effects against various diseases. In the present study, a bioanalytical method was developed for XH in rat plasma using reverse phase high performance liquid chromatography. The validation of the method was performed as per ICH M10 guidelines using curcumin as an internal standard. The Isocratic elution method was used with a run time of 10 min, wherein the mobile phase ratio 0.1% v/v OPA (A): Methanol (B) was 15:85 v/v at flow rate 0.8 mL/min and injection volume of 20 µL. The chromatograms of XH and curcumin was recorded at a wavelength of 370 nm. The retention time for XH and curcumin was 7.4 and 5.8 min, respectively. The spiked XH from plasma was extracted by the protein precipitation method. The developed method was linear with R2 value of 0.9996 over a concentration range of 50–250 ng/mL along with LLOQ. The results of all the validation parameters are found to be within the accepted limits with %RSD value less than 2 and the percentage recovery was found to be greater than 95%. Based on the %RSD and percentage recovery results it was confirmed that the method was precise and accurate among the study replicates. LOD and LOQ values in plasma samples were found to be 8.49 ng/mL and 25.73 ng/mL, respectively. The stability studies like freeze thaw, short term and long-term stability studies were also performed, %RSD and percentage recovery of the XH from plasma samples were within the acceptable limits. Therefore, the developed bioanalytical method can be used effectively for estimation of XH in plasma samples.

Fluorescent molecules absorb photons of specific wavelengths and emit a longer wavelength photon within nanoseconds. Recently, fluorescent materials have been widely used in the life and material sciences. Fluorescently labelled heterocyclic compounds are useful in bioanalytical applications, including in vivo imaging, high throughput screening, diagnostics, and light-emitting diodes. These compounds have various therapeutic properties, including antifungal, antitumor, antimalarial, anti-inflammatory, and analgesic activities. Different neutral fluorescent markers containing nitrogen heterocycles (quinolones, azafluoranthenes, pyrazoloquinolines, etc.) have several electrochemical, biological, and nonlinear optic applications. Photodynamic therapy (PDT), which destroys tumors and keeps normal tissues safe, works in the presence of molecular oxygen with light and a photosensitizing drugs (dye) to obtain a therapeutic effect. These compounds can potentially be effective templates for producing devices used in biological research. Blending crown compounds with fluorescent residues to create sensors has been frequently investigated. Florescent heterocyclic compounds (crown ether) increase metal solubility in non-aqueous fluids, broadening the application window. Fluorescent supramolecular polymers have widespread use in fluorescent materials, fluorescence probing, data storage, bio-imaging, drug administration, reproduction, biocatalysis, and cancer treatment. The employment of fluorophores, including organic chromophores and crown ethers, which have high selectivity, sensitivity, and stability constants, opens up new avenues for research. Fluorescent organic compounds are gaining importance in the biological world daily because of their diverse functionality with remarkable structural features and positive properties in the fields of medicine, photochemistry, and spectroscopy.

The present work was aimed at studying the biosorption of two important heavy metals, viz. Pb and Cr, using defatted seed residue of Cucumis melo as biosorbent. As this study for the biosorption of the selected biosorbent is being carried out for the first time, optimization of the% sorption was carried out with the help of Taguchi method. Three most influential experimental factors were taken into account for this purpose, including the amount of sorbent, amount of sorbate and shaking time. For Pb, maximum% sorption was found to be 94.1%, using 2 g of sorbent and 5 ppm of sorbate after 2 h of shaking. Similarly, for Cr, maximum% sorption was 92.5% using 2 g of sorbent, 10 ppm of sorbate and 3 h of shaking. For Pb, the highest% contribution, which was determined by ANOVA, was given by the amount of sorbate (54.7%) followed by the amount of sorbent (38.8%) and the least contribution was given by the shaking time (6.47%). Similarly, for Cr, the highest% contribution, which was determined by ANOVA, was given by the amount of sorbate (75%) followed by the amount of sorbent (16%) and the least contribution was given by the shaking time (8.65%). Kinetic and isothermal studies were also performed to understand the nature of adsorption mechanism. For this purpose, linear and non-linear forms of three sorption isotherms were employed including Freundlich, Langmuir and Dubnin–Radushkevich isotherm. From these observations, it can be concluded that the defatted seed residue of Cucumis melo can be regarded as a novel, renewable, green and cost-effective biosorbent for removal of heavy metals from wastewater.

In the search for new bioactive agents against the infectious pathogen responsible for the neglected tropical disease (NTD) mycetoma, we tested a collection of 27 essential oils (EOs) in vitro against Madurella mycetomatis, the primary pathogen responsible for the fungal form of mycetoma, termed eumycetoma. Among this series, the EO of Santalum album (Santalaceae), i.e., East Indian sandalwood oil, stood out prominently with the most potent inhibition in vitro. We, therefore, directed our research toward 15 EOs of Santalum species of different geographical origins, along with two samples of EOs from other plant species often commercialized as "sandalwood oils". Most of these EOs displayed similar strong activity against M. mycetomatis in vitro. All tested oils were thoroughly analyzed by GC-QTOF MS and most of their constituents were identified. Separation of the sandalwood oil into the fractions of sesquiterpene hydrocarbons and alcohols showed that its activity is associated with the sesquiterpene alcohols. The major constituents, the sesquiterpene alcohols (Z)-α- and (Z)-β-santalol were isolated from the S. album oil by column chromatography on AgNO3-coated silica. They were tested as isolated compounds against the fungus, and (Z)-α-santalol was about two times more active than the β-isomer. [ABSTRACT FROM AUTHOR]

The chemotherapy of tumors is frequently limited by the development of resistance and severe side effects. Phytochemicals may offer promising candidates to meet the urgent requirement for new anticancer drugs. We screened 69 phytochemicals, and focused on gedunin to analyze its molecular modes of action. Pearson test-base correlation analyses of the log10IC50 values of 55 tumor cell lines of the National Cancer Institute (NCI), USA, for gedunin with those of 91 standard anticancer agents revealed statistically significant relationships to all 10 tested microtubule inhibitors. Thus, we hypothesized that gedunin may be a novel microtubule inhibitor. Confocal microscopy, cell cycle measurements, and molecular docking in silico substantiated our assumption. Agglomerative cluster analyses and the heat map generation of proteomic data revealed a subset of 40 out of 3171 proteins, the expression of which significantly correlated with sensitivity or resistance for the NCI cell line panel to gedunin. This indicates the complexity of gedunin’s activity against cancer cells, underscoring the value of network pharmacological techniques for the investigation of the molecular modes of drug action. Finally, we correlated the transcriptome-wide mRNA expression of known drug resistance mechanism (ABC transporter, oncogenes, tumor suppressors) log10IC50 values for gedunin. We did not find significant correlations, indicating that gedunin’s anticancer activity might not be hampered by classical drug resistance mechanisms. In conclusion, gedunin is a novel microtubule-inhibiting drug candidate which is not involved in multidrug resistance mechanisms such as other clinically established mitotic spindle poisons.

Aim: A monoterpene and bioactive component of the plant Rhodiola rosea (R. rosea), rosiridin has beneficial effects on the human central nervous system and enhances brain function. The goal of this scientific study was to determine if rosiridin might shield rats from neurocognitive problems induced by scopolamine. Methods: To track the potential toxicities in rats, the acute toxicity in rats was clarified. Rosiridin at a dose of 10 mg/kg was tested in rats for 14 days. At the conclusion of the investigation, behavioral parameters that were used to identify the rats’ cognitive and motor abilities were evaluated. Several biochemical parameters were estimated using the prepared homogenate, including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), radical scavengers produced by the body (Catalase-CAT, superoxide dismutase-SOD, and reduced glutathione-GSH), indicators of oxidative and nitrative burnout, pro-inflammatory (Interleukins- IL-1β, IL-6, interferon gamma IFN-ꝩ, and tumor necrosis factor-TNF-α), and cell apoptosis caspases 3 and 9. Results and Conclusion: A significant behavioral parameter restoration was seen in the rosiridin-treated group, including reduction in latency time during acquisition and retention trial in the Morris water maze test, and percentage of spontaneous alterations in the y-maze test, when compared to the disease control group that received scopolamine; rosiridin also altered the oxidative stress and neuroinflammatory markers, as well as restoring Ach and ChAT activities and normalizing GSH, SOD, MDA, TNF-α, nitrate, IL-1β, IL-6, IFN-ꝩ, caspases 3 and 9 levels. The results imply that rosiridin limits the effect of scopolamine on rat cognitive function.

The α-glucosidase enzyme, located in the brush border of the small intestine, is responsible for overall glycemic control in the body. It hydrolyses the 1,4-linkage in the carbohydrates to form blood-absorbable monosaccharides that ultimately increase the blood glucose level. α-Glucosidase inhibitors (AGIs) can reduce hydrolytic activity and help to control type 2 diabetes. Aiming to achieve this, a novel series of 1-benzyl-3-((2-substitutedphenyl)amino)-2-oxoethyl)-2-(morpholinomethyl)-1H-benzimidazol-3-ium chloride was synthesized and screened for its α-glucosidase inhibitory potential. Compounds 5d, 5f, 5g, 5h and 5k exhibited better α-glucosidase inhibitions compared to the standard drug (acarbose IC50 = 58.8 ± 0.012 µM) with IC50 values of 15 ± 0.030, 19 ± 0.060, 25 ± 0.106, 21 ± 0.07 and 26 ± 0.035 µM, respectively. Furthermore, the molecular docking studies explored the mechanism of enzyme inhibitions by different 1,2,3-trisubstituted benzimidazolium salts via significant ligand–receptor interactions.

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = −7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = −7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.

ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm–multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69–0.87, F = 403.46–292.11, etc., internal validation parameters; Q2LOO = 0.69–0.86, Q2LMO = 0.69–0.86, CCCcv = 0.82–0.93, etc., or external validation parameters Q2F1 = 0.64–0.82, Q2F2 = 0.63–0.82, Q2F3 = 0.65–0.81, R2ext = 0.65–0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.

Carvedilol (CAR), a racemic lipophilic aryloxy propanolamine, acts as a selective α1-adrenoreceptor antagonist and a nonselective β-adrenoreceptor antagonist. CAR metabolism mainly produces three active metabolites: desmethyl carvedilol (DMC), 4′-hydroxy carvedilol (4′OHC) and 5′-hydroxy carvedilol (5′OHC). The oxidative S-(-)-metabolites contribute to the β-antagonistic effect, yet not to the α-antagonistic effect to be observed after drug dosage. Therefore, the three β-adrenoceptor blocking metabolites, which are structurally closely related to the parent CAR, are included into the development of a bioanalytical quantitative method for all major active species relevant with respect to adrenoceptor-blockade. Because of the given pharmacological profile, resolution of the enantiomers of carvedilol, of 4′- and 5′-hydroxy carvedilol as well as of DMC, is mandatory. The current study aims to determine the response surface for the enantiomer separation of the parent CAR as well as the major metabolites on a suitable chiral stationary phase. Design of experiment approach (DoE) was utilized in an initial screening phase followed by central-composite design for delimitation of the response surface for resolution of the four enantiomeric pairs in least run time. The impact of chromatographic variables (composition and percentage of organic modifier(s), buffer type, buffer pH, flow rate) on critical peaks resolution and adjusted retention time was evaluated, in order to select the most significant critical quality attributes. On this basis, a robust UHPLC-UV method was developed and optimized for the simultaneous, enantioselective determination of CAR along with its major active metabolites (4′OHC, 5′OHC, and DMC) on Chiralpak IBN-5. The optimized UHPLC-UV method (which includes metoprolol as the internal standard) was validated according to the ICH M10 guidelines for bioanalytical methods and proven to be linear, precise, accurate, and robust. The validated assay was applied to plasma samples from cardiovascular patients treated with rac-CAR (blood randomly drawn at different times after oral CAR intake). In order to provide more insight into the mechanism of the enantiomer separation of CAR and its metabolites on the CSP, docking experiments were performed. Molecular simulation studies suggest the chiral recognition to be mainly due to different binding poses of enantiomers of the same compound.

The current study evaluated the effect of pomegranate peel-based edible coating on chicken nuggets in order to develop a functional and safe product, high in nutritional value. For this purpose, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and total phenolic content (TPC) assays were performed to check the potential antioxidant activity of chicken nuggets; microbial control, including total aerobic count and coliforms population, was performed for quality and safety purposes; and thiobarbituric acid reactive substances (TBARS) and peroxide value (POV) were performed to determine the oxidative stability of chicken nuggets. Different treatments were applied at different storage periods (0th, 7th, 14th and 21st day). The higher value of total aerobic count (5.09 ± 0.05 log CFU/g) and coliforms (3.91 ± 0.06 log CFU/g) were obtained for the uncoated samples, while the lower population was enumerated in the combination of sodium alginate (SA) and pomegranate peel powder (PPP). However, DPPH (64.65 ± 2.15%) and TPC (135.66 ± 3.07 GAE/100 g) values were higher in the coated chicken nuggets (SA (1.5%) and PPP (1.5%)) and lowest in the control samples. The higher value of TBARS (1.62 ± 0.03 MDA/kg) and POV (0.92 ± 0.03 meq peroxide/kg) were observed in the uncoated chicken nuggets. In the Hunter color system, L*, a*, and b* peak values were determined in the coated chicken nuggets with SA (1.5%) + PPP (1.5%) at the 21st day of storage. The uncoated chicken nuggets had different sensory characteristics (appearance, color, taste, texture, and overall acceptability) compared to the coated samples. Conclusively, coating based on the combination of SA (1.5%) and PPP (1.5%) increased the quality, safety, and nutritional properties of chicken nuggets.

The microscale thermophoresis (MST) technique was utilized to investigate lactoferrin–drug interaction with the iron chelator, deferiprone, using label-free system. MST depends on the intrinsic fluorescence of one interacting partner. The results indicated a significant interaction between lactoferrin and deferiprone. The estimated binding constant for the lactoferrin–deferiprone interaction was 8.9 × 10−6 ± 1.6, SD, which is to be reported for the first time. Such significant binding between lactoferrin and deferiprone may indicate the potentiation of the drug secretion into a lactating mother’s milk. The technique showed a fast and simple approach to study protein–drug interaction while avoiding complicated labeling procedures. Moreover, the binding behavior of deferiprone within the binding sites of lactoferrin was investigated through molecular docking which reflected that deferiprone mediates strong hydrogen bonding with ARG121 and ASP297 in pocket 1 and forms H-bond and ionic interaction with ASN640 and ASP395, respectively, in pocket 2 of lactoferrin. Meanwhile, iron ions provide ionic interaction with deferiprone in both of the pockets. The molecular dynamic simulation further confirmed that the binding of deferiprone with lactoferrin brings conformational changes in lactoferrin that is more energetically stable. It also confirmed that deferiprone causes positive correlation motion in the interacting residues of both pockets, with strong negative correlation motion in the loop regions, and thus changes the dynamics of lactoferrin. The MM-GBSA based binding free energy calculation revealed that deferiprone exhibits ∆G TOTAL of −63,163 kcal/mol in pocket 1 and −63,073 kcal/mol in pocket 2 with complex receptor–ligand difference in pocket 1 and pocket 2 of −117.38 kcal/mol and −111.54 kcal/mol, respectively, which in turn suggests that deferiprone binds more strongly in the pocket 1. The free energy landscape of the lactoferrin–deferiprone complex also showed that this complex remains in a high energy state that confirms the strong binding of deferiprone with the lactoferrin. The current research concluded that iron-chelating drugs (deferiprone) can be transported from the mother to the infant in the milk because of the strong attachment with the lactoferrin active pockets.

Using 84 structurally diverse and experimentally validated LSD1/KDM1A inhibitors, quantitative structure–activity relationship (QSAR) models were built by OECD requirements. In the QSAR analysis, certainly significant and understated pharmacophoric features were identified as critical for LSD1 inhibition, such as a ring Carbon atom with exactly six bonds from a Nitrogen atom, partial charges of lipophilic atoms within eight bonds from a ring Sulphur atom, a non-ring Oxygen atom exactly nine bonds from the amide Nitrogen, etc. The genetic algorithm–multi-linear regression (GA-MLR) and double cross-validation criteria were used to create robust QSAR models with high predictability. In this study, two QSAR models were developed, with fitting parameters like R2 = 0.83–0.81, F = 61.22–67.96, internal validation parameters such as Q2LOO = 0.79–0.77, Q2LMO = 0.78–0.76, CCCcv = 0.89–0.88, and external validation parameters such as, R2ext = 0.82 and CCCex = 0.90. In terms of mechanistic interpretation and statistical analysis, both QSAR models are well-balanced. Furthermore, utilizing the pharmacophoric features revealed by QSAR modelling, molecular docking experiments corroborated with the most active compound’s binding to the LSD1 receptor. The docking results are then refined using Molecular dynamic simulation and MMGBSA analysis. As a consequence, the findings of the study can be used to produce LSD1/KDM1A inhibitors as anticancer leads.

Using traditional weight-loss tests, as well as different electrochemical techniques (potentiodynamic polarization and electrochemical impedance spectroscopy), we investigated the corrosion-inhibition performance of 2,2′-(1,4-phenylenebis(methanylylidene)) bis(N-(3-methoxyphenyl) hydrazinecarbothioamide) (PMBMH) as an inhibitor for mild steel in a 1 M hydrochloric acid solution. The maximum protection efficacy of 0.0005 M of PMBMH was 95%. Due to the creation of a protective adsorption layer instead of the adsorbed H2O molecules and acidic chloride ions, the existence of the investigated inhibitor reduced the corrosion rate and increased the inhibitory efficacy. The inhibition efficiency increased as the inhibitor concentration increased, but it decreased as the temperature increased. The PMBMH adsorption mode followed the Langmuir adsorption isotherm, with high adsorption-inhibition activity. Furthermore, the value of the ∆Gadso indicated that PMBMH contributed to the physical and chemical adsorption onto the mild-steel surface. Moreover, density functional theory (DFT) helped in the calculation of the quantum chemical parameters for finding the correlation between the inhibition activity and the molecular structure. The experimental and theoretical findings in this investigation are in good agreement.