Rocephin-graphene oxide-silver nanocomposites: A versatile platform for biomedical applications.

For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts.

Hole interactions of aerogen oxides with Lewis bases: an insight into σ-hole and lone-pair-hole interactions.

σ-Hole and lone-pair (lp)-hole interactions of aerogen oxides with Lewis bases (LB) were comparatively inspected in terms of quantum mechanics calculations. The ZOn ⋯ LB complexes (where Z = Kr and Xe, n = 1, 2, 3 and 4, and LB = NH3 and NCH) showed favourable negative interaction energies. The complexation features were explained in light of σ-hole and lp-hole interactions within optimum distances lower than the sum of the respective van der Waals radii. The emerging findings outlined that σ-hole interaction energies generally enhanced according to the following order: KrO4 ⋯ < KrO⋯ < KrO3⋯ < KrO2⋯LB and XeO4⋯ < XeO⋯ < XeO2⋯ < XeO3⋯LB complexes with values ranging from -2.23 to -12.84 kcal mol-1. Lp-hole interactions with values up to -5.91 kcal mol-1 were shown. Symmetry-adapted perturbation theory findings revealed the significant contributions of electrostatic forces accounting for 50-65% of the total attractive forces within most of the ZOn⋯LB complexes. The obtained observations would be useful for the understanding of hole interactions, particularly for the aerogen oxides, with application in supramolecular chemistry and crystal engineering.

Sigma-Hole and Lone-Pair-Hole Site-Based Interactions of Seesaw Tetravalent Chalcogen-Bearing Molecules with Lewis Bases.

For the first time, sigma (σ)- and lone-pair (lp)-hole site-based interactions of SF4 and SeF4 molecules in seesaw geometry with NH3 and FH Lewis bases were herein comparatively investigated. The obtained findings from the electrostatic potential analysis outlined the emergence of sundry holes on the molecular entity of the SF4 and SeF4 molecules, dubbed the σ- and lp-holes. The energetic viewpoint announced splendid negative binding energy values for σ-hole site-based interactions succeeded by lp-hole analogues, which were found to be -9.21 and -0.50 kcal/mol, respectively, for SeF4···NH3 complex as a case study. Conspicuously, a proper concurrence between the strength of chalcogen σ-hole site-based interactions and the chalcogen's atomic size was obtained, whereas a reverse pattern was proclaimed for the lp-hole counterparts. Further, a higher preference for the YF4···NH3 complexes with elevated negative binding energy was promulgated over the YF4···FH ones, indicating the eminent role of Lewis basicity. The indications of the quantum theory of atoms in molecules generally asserted the closed-shell nature of all the considered interactions. The observation of symmetry-adapted perturbation theory revealed the substantial contributing role of the electrostatic forces beyond the occurrence of σ-hole site-based interactions. In comparison, the dispersion forces were specified to govern the lp-hole counterparts. Such emerging findings would be a gate for the fruitful forthcoming applications of chalcogen bonding interactions in crystal engineering and biological systems.

Green synthesis of cobalt ferrite and Mn doped cobalt ferrite nanoparticles: Anticancer, antidiabetic and antibacterial studies.

BACKGROUND: CoFe2O4 are important magnetic NPs with high coercivity and moderate magnetization. These properties of CoFe2O4 NPs show variation when doped with various metals. Recent studies explained that Cobalt ferrites doped with metal ion like Mn+2, have attracted increasing attention in many applications, particularly in biomedical applications. A relatively simple way is employing plants and their extracts as precursors instead of toxic chemicals to produce NPs with desirable characteristic. In current study we report green synthesis and characterization of magnetic (CoFe2O4, MnCoFe2O4, CoFe2O4@S.C, MnCoFe2O4@S.C) nanoparticles using ethanolic extract of Swertia Chirata. To enhance application as biocompatible magnetic nano drug delivery vector and cell targeting efficacy of drugs, Glimepiride (GLM), Dexamethasone (DXM), Fexofenadine (FEX) and Levofloxacin (LVX) 1were loaded on synthesized NPs. Synthesized CFNPs has been broadly characterized and applied for in vitro anticancer, antidiabetic and antibacterial potential. METHODS: For synthesis of CoFe2O4 (CF), CoMnFe2O4 (CFM), CoFe2O4@S.C (SCF) & CoMnFe2O4 @S.C (SCFM), stochiometric amounts 5 mmol of CoCl2·6 H2O (0.284 g) and 10 mmol FeCl3·6 H2O (0.378 g) were dissolved in 13 mL of deionized water. To this sodium acetate (3.05 g) and urea (0.6 g) were added until complete dissolution. Afterward n-heptane was added, and contents were then transferred to Teflon lining autoclave at 180 °C for 4 h. Black powder CoFe2O4 NPs after washing, were dried and calcined at 450 oC for 2 h. RESULTS: XRD diffractogram of CF have proved the single-phase cubic spinel structure formation for all samples. Swertia Chirata formulations were shown to have effective in vitro antidiabetic activity. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. SCF showed that the value slightly higher than 16 µg/mL compared to standard. Drug loaded CFNPs (L-CFNPs, F-CFNPs, D-CFNPs & G-CFNPs) also effectively inhibited α-glucosidase. IC50 value for CFNPs inhibition of α-glucosidase was 12.4 µg/mL. All synthesized CF NPs showed cytotoxic potential against breast cancer cells MCF-7. About 50-60% cell viability and cytotoxicity 40% were observed for bare CFNPs as compare to Doxorubicin with related toxicity 80% and 20% cell viability. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. CFM, SCF, SCFM were active against S. aureus at concentration 100 µg/mL, 100 µg/mL, and 50 µg/mL respectively. CONCLUSION: The synthesized CF NPs showed significant cytotoxic potential against MCF-7 breast cancer cell line. Further, drug loaded samples displayed lesser cell viability and slightly increased cytotoxicity in range of 40-50% in comparison with bare CFNPs. However, higher toxicity was observed for CFMGS towards MCF-7 cells with results nearly equal to Doxorubicin with significant decrease in viability. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain.

Adsorption Features of Tetrahalomethanes (CX4; X = F, Cl, and Br) on ß12 Borophene and Pristine Graphene Nanosheets: A Comparative DFT Study.

The potentiality of the ß12 borophene (ß12) and pristine graphene (GN) nanosheets to adsorb tetrahalomethanes (CX4; X = F, Cl, and Br) were investigated using density functional theory (DFT) methods. To provide a thorough understanding of the adsorption process, tetrel (XC-X3∙∙∙ß12/GN)- and halogen (X3C-X∙∙∙ß12/GN)-oriented configurations were characterized at various adsorption sites. According to the energetic manifestations, the adsorption process of the CX4∙∙∙ß12/GN complexes within the tetrel-oriented configuration led to more desirable negative adsorption energy (Eads) values than that within the halogen-oriented analogs. Numerically, Eads values of the CBr4∙∙∙Br1@ß12 and T@GN complexes within tetrel-/halogen-oriented configurations were -12.33/-8.91 and -10.03/-6.00 kcal/mol, respectively. Frontier molecular orbital (FMO) results exhibited changes in the EHOMO, ELUMO, and Egap values of the pure ß12 and GN nanosheets following the adsorption of CX4 molecules. Bader charge transfer findings outlined the electron-donating property for the CX4 molecules after adsorbing on the ß12 and GN nanosheets within the two modeled configurations, except the adsorbed CBr4 molecule on the GN sheet within the tetrel-oriented configuration. Following the adsorption process, new bands and peaks were observed in the band structure and density of state (DOS) plots, respectively, with a larger number in the case of the tetrel-oriented configuration than in the halogen-oriented one. According to the solvent effect affirmations, adsorption energies of the CX4∙∙∙ß12/GN complexes increased in the presence of a water medium. The results of this study will serve as a focal point for experimentalists to better comprehend the adsorption behavior of ß12 and GN nanosheets toward small toxic molecules.

Ameliorative effect of two structurally divergent hydrazide derivatives against DSS-induced colitis by targeting Nrf2 and NF-κB signaling in mice.

The environmental factors and genetic vulnerability trigger the inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease. Furthermore, the oxidative stress and inflammatory cytokines have been implicated in the aggravation of the IBDs. The aim of the present study was to investigate the effect of N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (NCHDH and NTHDH) compounds against the DSS-induced colitis in mice. The colitis was induced by 5% dextran sulfate sodium (DSS) dissolved in normal saline for 5 days. The effect of the NCHDH and NTHDH on the behavioral, biochemical, histological, and immunohistological parameters was assessed. The NCHDH and NTHDH treatment improved the behavioral parameters such as food intake, disease activity index, and diarrhea score significantly compared to DSS control. The NCHDH and NTHDH treatments significantly increased the antioxidant enzymes, whereas oxidative stress markers were markedly reduced. Similarly, the NCHDH and NTHDH treatments significantly suppressed the activity of nitric oxide (NO), myeloperoxidase (MPO), and eosinophil peroxidase (EPO). The histological studies showed a significant reduction in inflammation, immune cell infiltration, and fibrosis in the NCHDH- and NTHDH-treated groups. The immunohistochemical results demonstrated that NCHDH and NTHDH treatments markedly increase the expression level of Nrf2, HO-1 (hemeoxygenase-1), TRX (thioredoxin reductase), and IκB compared to the DSS-induced group. In the same way, the NCHDH and NTHDH significantly reduced the NF-κB and COX-2 (cyclooxygenase-2) expression levels. The NCHDH and NTHDH treatment significantly improved the symptoms associated with colitis via inducing antioxidants and attenuating oxidative stress markers.

External Electric Field Effect on the Strength of σ-Hole Interactions: A Theoretical Perspective in Like⋯Like Carbon-Containing Complexes.

For the first time, σ-hole interactions within like⋯like carbon-containing complexes were investigated, in both the absence and presence of the external electric field (EEF). The effects of the directionality and strength of the utilized EEF were thoroughly unveiled in the (F-C-F3)2, (F-C-H3)2, and (H-C-F3)2 complexes. In the absence of the EEF, favorable interaction energies, with negative values, are denoted for the (F-C-F3)2 and (H-C-F3)2 complexes, whereas the (F-C-H3)2 complex exhibits unfavorable interactions. Remarkably, the strength of the applied EEF exhibits a prominent role in turning the repulsive forces within the latter complex into attractive ones. The symmetrical nature of the considered like⋯like carbon-containing complexes eradicated the effect of directionality of the EEF. The quantum theory of atoms in molecules (QTAIM), and the noncovalent interaction (NCI) index, ensured the occurrence of the attractive forces, and also outlined the substantial contributions of the three coplanar atoms to the total strength of the studied complexes. Symmetry-adapted perturbation theory (SAPT) results show the dispersion-driven nature of the interactions.

Synthesis, X-ray diffraction analysis, quantum chemical studies and α-amylase inhibition of probenecid derived S-alkylphthalimide-oxadiazole-benzenesulfonamide hybrids.

Sulphonamide and 1,3,4-oxadiazole moieties are present as integral structural parts of many drugs and pharmaceuticals. Taking into account the significance of these moieties, we herein present the synthesis, single-crystal X-ray analysis, DFT studies, and α-amylase inhibition of probenecid derived two S-alkylphthalimide-oxadiazole-benzenesulfonamide hybrids. The synthesis has been accomplished in high yields. The final structures of both hybrids have been established completely with the help of different spectro-analytical techniques, including NMR, FTIR, HR-MS, and single-crystal X-ray diffraction analyses. In an effort to confirm the experimental findings, versatile quantum mechanical calculations and Hirshfeld Surface analysis have been performed. α-Amylase inhibition assay has been executed to investigate the enzyme inhibitory potential of both hybrids. The low IC50 value (76.92 ± 0.19 µg/mL) of hybrid 2 shows the good α-amylase inhibition potential of the respective compound. Ultimately, the binding affinities and features of the two hybrids are elucidated utilising a molecular docking technique against the α-amylase enzyme.

Effects of Artemisia macrocephala Jacquem on Memory Deficits and Brain Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Different species of Artemisia have been reported to have therapeutic potential in treating various health disorders, including diabetes and memory dysfunction. The present study was planned to evaluate the effects of Artemisia macrocephala Jacquem crude extract and its subfractions as antiamnesic agents in streptozotocin-induced (STZ) diabetic mice. The in vivo behavioral studies were performed using the Y Maze test and novel object recognition test (NORT) test at doses of 100 and 200 mg/kg of crude extract and 75 and 150 mg/kg of fractions. The in vitro and ex vivo anticholinesterase activities, along with biochemical parameters (superoxide dismutase, catalase, glutathione and lipid peroxidation) in the brain, were evaluated. Blood glucose levels were monitored with a glucometer; crude extract and fractions reduced the glucose level considerably, with some differences in the extent of their efficacies. The crude extract and fractions demonstrated significant inhibitory activity against cholinesterases (AChE and BuChE) in vitro. Crude, chloroform and ethyl acetate extract were found to be more potent than the other fractions, with IC50 of Crd-Am = 116.36 ± 1.48 and 240.52 ± 1.35 µg/mL, Chl-Am = 52.68 ± 1.09 and 57.45 ± 1.39 µg/mL and Et-Am = 75.19 ± 1.02 and 116.58 ± 1.09 µg/mL, respectively. Oxidative stress biomarkers like superoxide dismutase, catalase and glutathione levels were elevated, whereas MDA levels were reduced by crude extract and all fractions with little difference in their respective values. The Y-maze test and novel object recognition test demonstrated declines in memory impairment in groups (n = 6) treated with crude extract and fractions as compared to STZ diabetic (amnesic) group. The most active fraction, Chl-Am, was also subjected to isolation of bioactive compounds; three compounds were obtained in pure state and designated as AB-I, AB-II and AB-III. Overall, the results of the study showed that Artemisia macrocephala Jacquem enhanced the memory impairment associated with diabetes, elevated acetylcholine levels and ameliorated oxidative stress. Further studies are needed to explore the beneficial role of the secondary metabolites isolated in the present study as memory enhancers. Toxicological aspects of the extracts are also important and need to be evaluated in other animal models.

σ-Hole and LP-Hole Interactions of Pnicogen···Pnicogen Homodimers under the External Electric Field Effect: A Quantum Mechanical Study.

σ-Hole and lone-pair (lp)-hole interactions within σ-hole···σ-hole, σ-hole···lp-hole, and lp-hole···lp-hole configurations were comparatively investigated on the pnicogen···pnicogen homodimers (PCl3)2, for the first time, under field-free conditions and the influence of the external electric field (EEF). The electrostatic potential calculations emphasized the impressive versatility of the examined PCl3 monomers to participate in σ-hole and lp-hole pnicogen interactions. Crucially, the sizes of σ-hole and lp-hole were enlarged under the influence of the positively directed EEF and decreased in the case of reverse direction. Interestingly, the energetic quantities unveiled more favorability of the σ-hole···lp-hole configuration of the pnicogen···pnicogen homodimers, with significant negative interaction energies, than σ-hole···σ-hole and lp-hole···lp-hole configurations. Quantum theory of atoms in molecules and noncovalent interaction index analyses were adopted to elucidate the nature and origin of the considered interactions, ensuring their closed shell nature and the occurrence of attractive forces within the studied homodimers. Symmetry-adapted perturbation theory-based energy decomposition analysis alluded to the dispersion force as the main physical component beyond the occurrence of the examined interactions. The obtained findings would be considered as a fundamental underpinning for forthcoming studies pertinent to chemistry, materials science, and crystal engineering.

Type I-IV Halogen⋯Halogen Interactions: A Comparative Theoretical Study in Halobenzene⋯Halobenzene Homodimers.

In the current study, unexplored type IV halogen⋯halogen interaction was thoroughly elucidated, for the first time, and compared to the well-established types I−III interactions by means of the second-order Møller−Plesset (MP2) method. For this aim, the halobenzene⋯halobenzene homodimers (where halogen = Cl, Br, and I) were designed into four different types, parodying the considered interactions. From the energetic perspective, the preference of scouted homodimers was ascribed to type II interactions (i.e., highest binding energy), whereas the lowest binding energies were discerned in type III interactions. Generally, binding energies of the studied interactions were observed to decline with the decrease in the σ-hole size in the order, C6H5I⋯IC6H5 > C6H5Br⋯BrC6H5 > C6H5Cl⋯ClC6H5 homodimers and the reverse was noticed in the case of type IV interactions. Such peculiar observations were relevant to the ample contributions of negative-belt⋯negative-belt interactions within the C6H5Cl⋯ClC6H5 homodimer. Further, type IV torsional trans → cis interconversion of C6H5X⋯XC6H5 homodimers was investigated to quantify the π⋯π contributions into the total binding energies. Evidently, the energetic features illustrated the amelioration of the considered homodimers (i.e., more negative binding energy) along the prolonged scope of torsional trans → cis interconversion. In turn, these findings outlined the efficiency of the cis configuration over the trans analog. Generally, symmetry-adapted perturbation theory-based energy decomposition analysis (SAPT-EDA) demonstrated the predominance of all the scouted homodimers by the dispersion forces. The obtained results would be beneficial for the omnipresent studies relevant to the applications of halogen bonds in the fields of materials science and crystal engineering.

N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) attenuate DMBA-induced breast cancer via Nrf2/NF-κB/apoptosis signaling.

The present study investigated the effect of the N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) against breast cancer using in vitro and in vivo approaches. The NCHDH and NTHDH significantly inhibited the growth of the MCF-7 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The NCHDH and NTHDH treatment significantly inhibited the tumor size, tumor weight, and tumor volume, while it enhanced the survival and tumor free survival rate following 7,12-Dimethylbenz[a]anthracene (DMBA)-induced breast cancer. The NCHDH and NTHDH markedly attenuated the oxidative stress markers and induced the antioxidant level. The enzyme-linked immunosorbent assay (ELISA) showed significant reduction in the inflammatory cytokines production compared with the DMBA control. The NCHDH and NTHDH treatment significantly improved the histological features using hematoxylin and eosin (H and E) staining, Masson's trichrome, PAS (periodic acid Schiff), and Toluidine blue staining compared with the DMBA-induced group. The NCHDH and NTHDH treatment improved the hematological and serological parameters following DMBA-induced breast tumor compared with DMBA-induced group. Furthermore, the NCHDH and NTHDH treatment significantly enhanced the antioxidants signaling proteins such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Heme oxygenase 1 (HO-1). The NCHDH and NTHDH enhanced the inhibitor of NF-κB (IκB) level, while it attenuated the NF-κB level. Similarly, the NCHDH and NTHDH showed marked increase in the apoptosis proteins such as Caspase-3, Caspase-9, and Bcl-2 Associated X-protein (Bax), while it inhibited the B-cell lymphoma 2 (Bcl-2) expression. In conclusion, the NCHDH and NTHDH significantly improved the DMBA-induced breast cancer via attenuating oxidative stress and inflammatory cytokines.

Borophene and Pristine Graphene 2D Sheets as Potential Surfaces for the Adsorption of Electron-Rich and Electron-Deficient π-Systems: A Comparative DFT Study.

The versatility of striped borophene (sB), ß12 borophene (ß12), and pristine graphene (GN) to adsorb π-systems was comparatively assessed using benzene (BNZ) and hexafluorobenzene (HFB) as electron-rich and electron-deficient aromatic π-systems, respectively. Using the density functional theory (DFT) method, the adsorption process of the π-systems on the investigated 2D sheets in the parallel configuration was observed to have proceeded more favorably than those in the vertical configuration. According to the observations of the Bader charge transfer analysis, the π-system∙∙∙sB complexes were generally recorded with the largest contributions of charge transfer, followed by the π-system∙∙∙ß12 and ∙∙∙GN complexes. The band structures of the pure sheets signaled the metallic and semiconductor characters of the sB/ß12 and GN surfaces, respectively. In the parallel configuration, the adsorption of both BNZ and HFB showed more valence and conduction bands compared to the adsorption in the vertical configuration, revealing the prominent preferentiality of the anterior configuration. The density-of-states (DOSs) results also affirmed that the adsorption process of the BNZ and HFB on the surface of the investigated 2D sheets increased their electrical properties. In all instances, the sB and ß12 surfaces demonstrated higher adsorptivity towards the BNZ and HFB than the GN analog. The findings of this work could make a significant contribution to the deep understanding of the adsorption behavior of aromatic π-systems toward 2D nanomaterials, leading, in turn, to their development of a wide range of applications.

In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1-F6) and flavonols (OF1-OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 µg/mL and 25.54 ± 1.21 µg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 µg/mL and 122.33 ± 1.98 µg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Naturally occurring plant-based anticancerous candidates as prospective ABCG2 inhibitors: an in silico drug discovery study.

ATP-binding cassette transporter G2 (ABCG2) is an efflux transporter related to the clinical multidrug resistance (MDR) phenomenon. Identifying ABCG2 inhibitors could help discover extraordinary curative strategies for carcinoma remediation. Hitherto, there is no medication drug inhibiting ABCG2 transporter, notwithstanding that a considerable number of drugs have been submitted to clinical-trial and investigational phases. In the search for unprecedented chemical compounds that could inhibit the ABCG2 transporter, an in silico screening was conducted on the Naturally Occurring Plant-based Anticancer Compound-Activity-Target (NPACT) database containing 1574 compounds. Inhibitor-ABCG2 binding affinities were estimated based on molecular docking and molecular minimization (MM) calculations and compared to a co-crystallized inhibitor (BWQ) acting as a reference inhibitor. Molecular dynamics (MD) simulations pursued by molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations were further executed for compounds with MM-GBSA//MM binding energies lower than BWQ (calc. - 60.5 kcal/mol). NPACT00968 and NPACT01545 demonstrated auspicious inhibitory activities according to binding affinities (ΔGbinding) over the 100 ns MD simulations that were nearly one and a half folds compared to BWQ (- 100.4, - 94.7, and - 62.9 kcal/mol, respectively). Throughout the 100 ns MD simulations, structural and energetical analyses unveiled outstanding stability of the ABCG2 transporter when bound with NPACT00968 and NPACT01545. In silico calculations hold a promise for those two inhibitors as drug candidates of ABCG2 transporter and emphasize that further in vitro and in vivo experiments are guaranteed.

Exploring Toxins for Hunting SARS-CoV-2 Main Protease Inhibitors: Molecular Docking, Molecular Dynamics, Pharmacokinetic Properties, and Reactome Study.

The main protease (Mpro) is a potential druggable target in SARS-CoV-2 replication. Herein, an in silico study was conducted to mine for Mpro inhibitors from toxin sources. A toxin and toxin-target database (T3DB) was virtually screened for inhibitor activity towards the Mpro enzyme utilizing molecular docking calculations. Promising toxins were subsequently characterized using a combination of molecular dynamics (MD) simulations and molecular mechanics-generalized Born surface area (MM-GBSA) binding energy estimations. According to the MM-GBSA binding energies over 200 ns MD simulations, three toxins-namely philanthotoxin (T3D2489), azaspiracid (T3D2672), and taziprinone (T3D2378)-demonstrated higher binding affinities against SARS-CoV-2 Mpro than the co-crystalized inhibitor XF7 with MM-GBSA binding energies of -58.9, -55.9, -50.1, and -43.7 kcal/mol, respectively. The molecular network analyses showed that philanthotoxin provides a ligand lead using the STRING database, which includes the biochemical top 20 signaling genes CTSB, CTSL, and CTSK. Ultimately, pathway enrichment analysis (PEA) and Reactome mining results revealed that philanthotoxin could prevent severe lung injury in COVID-19 patients through the remodeling of interleukins (IL-4 and IL-13) and the matrix metalloproteinases (MMPs). These findings have identified that philanthotoxin-a venom of the Egyptian solitary wasp-holds promise as a potential Mpro inhibitor and warrants further in vitro/in vivo validation.

R•-hole interactions of group IV-VII radical-containing molecules: A comparative study.

For the first time, the potentiality of the sp2-hybridized group IV-VII radical (R•)-containing molecules to participate in R•-hole interactions was comparatively assessed using •SiF3,•POF2, •SO2F, and •ClO3 models in the trigonal pyramidal geometry. In that spirit, a plethora of quantum mechanical calculations was performed at the MP2/aug-cc-pVTZ level of theory. According to the results, all the investigated R•-containing molecules exhibited potent versatility to engage in R•-hole … Lewis base interactions with significant negative binding energies for the NCH-based complexes. The strength of R•-hole interactions was perceived to obey the •ClO3 … > â€¢SO2F … > â€¢POF2 … > â€¢SiF3 … Lewis base order, outlining an inverse correlation between the binding energy and the atomic size of the R•-hole donor. Benchmarking of the binding energy at the CCSD/CBS(T) computational level was executed for all the explored interactions and addressed an obvious similarity between the MP2 and CCSD energetic findings. QTAIM analysis critically unveiled the closed-shell nature of the explored R•-hole interactions. SAPT-EDA proclaimed the reciprocal contributions of electrostatic and dispersion forces to the total binding energy. These observations demonstrate in better detail the nature of R•-hole interactions, leading to a convincing amelioration for versatile fields relevant to materials science and drug design.

Cytotoxicity, Anti-diabetic, and Hepato-protective Potential of Ajuga bracteosa-conjugated Silver Nanoparticles in Balb/c Mice.

BACKGROUND: Ajuga bracteosa is a traditional herb used against various diseases. OBJECTIVES: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). METHODS: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. RESULTS: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepatoprotective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity. CONCLUSION: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepatoprotective phytoconstituents, which could be used in the prevention of diseases.