Assessment of Drimia delagoensis (Jessop) Baker Total Phenol, Flavonoids Content and Antioxidant Activity of Both Bulb and Leaves.

Drimia delagoensis has been utilized for its medicinal properties since antiquity. The bulb and leaves are predominantly composed of secondary metabolites that exhibit biological activity. The quantification of total phenolic and flavonoid content, as well as the assessment of antioxidant activity was conducted using the Folin-Ciocalteus method, coulometric analysis, DPPH and the FRAP assays. The ethyl acetate, aqueous, and hexane extracts of the bulb exhibited significantly high total phenolic contents (167.9000±0.3376 µg GAE/mg, 56.2500±0.0043 µg GAE/mg, and 26.4000±0.0198 µg GAE/mg, respectively) compared to the ethyl acetate (49.4400±0.1341 µg QE/mg), aqueous (9.5200±0.1274 µg QE/mg), and hexane leaf extracts (1.8091±0.0049 µg QE/mg). On the other hand, the ethyl acetate leaf extract exhibited the highest antioxidant and free radical scavenging activity. The ethyl acetate extract of D. delagoensis, was identified as a significant source of natural antioxidants, and its use in the management of diabetic foot ulcers linked with oxidative stress is supported.

Exploring indigenous freshwater chlorophytes in integrated biophotovoltaic system for simultaneous wastewater treatment, heavy metal biosorption, CO2 biofixation and biodiesel generation.

The study explored the combined photosynthetic activities of two green microalgal species, Tetradesmus obliquus and Tetradesmus reginae, on an integrated biophotovoltaic (BPV) platform for simultaneous wastewater treatment, toxic metal biosorption, carbon biofixation, bioelectricity generation and biodiesel production. The experimental setup comprised of a dual-chambered BPV with copper anode surrounded by T. obliquus in BG11 media, and copper cathode with T. reginae in municipal wastewater separated by Nafion 117 membrane. The study reported a maximum power density of 0.344 Wm-2 at a cell potential of 0.415 V with external resistance of 1000 Ω and 0.3268 V maximum open-circuit voltage. The wastewater electrical conductivity and pH increased from 583 ± 22 to 2035 ± 29.31 mS/cm and 7.403 ± 0.174 to 8.263 ± 0.055 respectively, signifying increased photosynthetic and electrochemical activities. Residual nitrogen, phosphorus, chemical oxygen demand, arsenic, cadmium, chromium and lead removal efficiencies by T. reginae were 100%, 80.68%, 71.91%, 47.6%, 88.82%, 71.24% and 92.96%, respectively. T. reginae accumulated maximum biomass of 0.605 ± 0.033 g/L with a CO2 biosequestration rate of 0.166 ± 0.010 gCO2/L/day and 42.40 ± 1.166% lipid content. Methyl palmitate, methyl undecanoate and 13-octadecenoic acid with relative abundances of 37.24%, 24.80% and 12.02%, respectively were confirmed.

Exploiting the glycan receptor-binding site of PltB subunit in salmonella typhi toxin for novel inhibitors: An in-silico approach.

Salmonella typhi (S. typhi), a gram-negative bacterium responsible for gastroenteritis - typhoid - has continually evolved into drug-resistant strains with the most recent being the haplotype H58 strain. The haplotype H58 strain has spread across the globe causing outbreaks in countries such as Pakistan, Zimbabwe, and several underdeveloped regions located in parts of Asia, Central and Southern Africa. Treatment by conventional antibiotics is gradually failing as recorded in the affected countries, including Nigeria and Barcelona - Spain. Therefore, the research presented herein aims to identify novel compounds targeting the typhoid toxin of S. typhi which is responsible for several virulence factors associated with typhoid. In-silico methods that include virtual screening, molecular dynamics (MD) and computation of binding free energies were utilized. Our research identified furan derivatives as top-scoring lead compounds from a database of more than 1,5 million compounds curated from the ZINC20 database. Post docking analysis and trajectory analysis post-MD simulations showed that π - π interactions are vital to holding the ligand within the receptor pocket whereas hydrophobic and Van der Waals interactions are crucial for the overall bonding. Through docking, MD simulations and free energy computations, we hypothesize that ZINC000114543311, ZINC000794380763 and ZINC000158992484 (docking scores of -9.06, -8.20 and -8.12 in conjunction with ΔG values of -64.691, -63.670 and -59.024 kcal/mol, respectively) bear a great potential to pave the way to fighting antibiotic resistance for typhoid in both humans and animals. The compounds presented here can also be used as lead materials for designing other compounds targeting the Salmonella typhi toxin.

Energy and reactivity profile and proton affinity analysis of rimegepant with special reference to its potential activity against SARS-CoV-2 virus proteins using molecular dynamics.

Rimegepant is a new medicine developed for the management of chronic headache due to migraine. This manuscript is an attempt to study the various structural, physical, and chemical properties of the molecules. The molecule was optimized using B3LYP functional with 6-311G + (2d,p) basis set. Excited state properties of the compound were studied using CAM-B3LYP functional with same basis sets using IEFPCM model in methanol for the implicit solvent atmosphere. The various electronic descriptors helped to identify the reactivity behavior and stability. The compound is found to possess good nonlinear optical properties in the gas phase. The various intramolecular electronic delocalizations and non-covalent interactions were analyzed and explained. As the compound contain several heterocyclic nitrogen atoms, they have potential proton abstraction features, which was analyzed energetically. The most important result from this study is from the molecular docking analysis which indicates that rimegepant binds irreversibly with three established SARS-CoV-2 proteins with ID 6LU7, 6M03, and 6W63 with docking scores - 9.2988, - 8.3629, and - 9.5421 kcal/mol respectively. Further assessment of docked complexes with molecular dynamics simulations revealed that hydrophobic interactions, water bridges, and π-π interactions play a significant role in stabilizing the ligand within the binding region of respective proteins. MMGBSA-free energies further demonstrated that rimegepant is more stable when complexed with 6LU7 among the selected PDB models. As the pharmacology and pharmacokinetics of this molecule are already established, rimegepant can be considered as an ideal candidate with potential for use in the treatment of COVID patients after clinical studies.

Developing a simple box-behnken experimental design on the removal of doxorubicin anticancer drug using Fe3O4/graphene nanoribbons adsorbent.

This paper aims to develop a Box-Behnken experimental design system to optimize the removal process of doxorubicin anticancer drugs. For this goal, Fe3O4/graphene nanoribbons was selected as adsorbent and removal of doxorubicin anticancer drug optimized using Box-Behnken experimental design with a selection of four effective factors. A three-level, four-factor Box-Behnken experimental design was used to assess the relationship between removal percentage as a dependent variable with adsorption weight (0.0015-0.01 mg), pH (3-9), temperature (15-45 °C) and time (1-15 min) as independent variables. Optimized condition by Behnken experimental design (pH = 7.36; time = 15 min; adsorbent weight = 0.01 mg and temperature = 29.26 °C) improved removal of doxorubicin anticancer drug about 99.2% in aqueous solution. The dynamic behavior, adsorption properties and mechanism of doxorubicin molecule on Fe3O4/graphene nanoribbon were investigated based on ab initio molecular dynamics (AIMD) simulations and density functional theory calculations with dispersion corrections. A closer inspection of the adsorption configurations and binding energies revealed that π-π interactions were the driving force when the doxorubicin molecule adsorbed on Fe3O4/graphene nanoribbon. The observed negative adsorption energy signifies a favourable and exothermic adsorption process of the various adsorbate-substrate systems. Besides, AIMD and phonon dispersion calculations confirm the dynamic stability of Fe3O4/graphene nanoribbon.

Ligand-based pharmacophore modelling and virtual screening for the identification of amyloid-beta diagnostic molecules.

Currently, only three molecules, flutemetamol, florbetaben and florbetapir, have been approved for clinical use towards the definitive diagnosis of Alzheimer's disease (AD). Despite the clinically approved drugs' advantages, there still exists a need for new diagnostic molecules with improved properties (physicochemical and pharmacokinetic) in comparison to the current molecules in clinical use and research. In this work, we report a pharmacophore model and a quantitative structure activity relationship (QSAR) model, constructed from a series of 166 amyloid beta diagnostic compounds (targeting Alzheimer's disease) with the purpose of identifying functional groups influencing and predicting bioactivity. Subsequently, pharmacophore based virtual screening and QSAR predictions were used to identify new amyloid beta diagnostic molecules. In addition, docking and molecular dynamics simulations were conducted to explore the type and nature of interactions required for ligands to bind effectively in the binding regions of amyloid beta fibrils (PDB 2MXU). In our findings, the highest-ranked 4 feature pharmacophore model possessed one hydrogen bond acceptor, one hydrophobic feature and two ring features (AHRR). Systematically, the same dataset of molecules used for pharmacophore modelling was used to generate an atom-based 3D QSAR hypothesis to illustrate the activity relationship of amyloid-beta diagnostic molecules. The partial least squares (PLS) 3D QSAR model obtained showed good correlation as indicated by respective statistical parameters, R^2, Q^2 and Pearson values of 0.76, 0.72 and 0.86 respectively. Virtual screening against ZINC15 database and the ChemBridge CNS-Set yielded 7 molecules, 4 of which had satisfactory ADME properties. Docking and molecular dynamics simulations showed that hydrogen bonding, hydrophobic and π-π interactions are crucial towards the binding of ligands (as predicted by our pharmacophore and QSAR models) to amyloid beta fibrils. In conclusion, the findings of this work present a wealth of information that can be useful in future research towards identifying and design of new amyloid diagnostic molecules. The pharmacophore presented here can be used to filter independent databases to identify new structurally related molecules with improved activity whereas the QSAR model can be useful in predicting bioactivities of the predicted hits.

Composite 2D Nanointerfaces for Electrochemical Biosensing: An Experimental and Theoretical Study.

In this study, composite two-dimensional (2D) materials consisting of graphene (Gr) and tungsten disulfide (WS2) were coalesced with gold nanoparticles (AuNPs) through a self-assembly process to boost the conductivity of the resulting graphene-tungsten disulfide-gold nanoparticles (Gr-WS2-AuNPs) nanointerface structure. Structural and morphological characterization of the nanohybrid structure reveals crystalline thin flakelike agglomerates. Electrochemical characterization reveals an excellent electron transfer process for all the modified electrodes at the interface. The Gr/WS2/AuNPs/HRP/GCE modified bioelectrode exhibited a rapid electrobiocatalytic response in detecting H2O2 and a linear response from 0.40 to 23 mM, while 11.07 µA/mM/cm2 is the sensitivity value. This shows that the fabricated Gr/WS2/AuNPs/HRP interface structure is an excellent material for future developments in electrochemical biosensing and bioelectronics applications. The interactions, geometry, and energetic and electronic properties of H2O2 adsorption onto Gr/WS2/Au using the density functional theory (DFT) method have also been investigated along with the Grimme's DFT-D3 dispersion method. Different adsorption modes of the H2O2 molecule onto the Gr/WS2/Au surface were considered. In almost all the cases, the adsorption was found to be energetically favorable and chemisorbed, with energies ranging from -2.198 to -3.782 eV. It was found that the W 5d, S 3p, and Au 6s orbitals play a vital role in the adsorption process. The H2O2 adsorption on Gr/WS2/Au remarkably decreases its work function, thereby increasing the field electron emission from the H2O2 molecule to Gr/WS2/Au.

Computational investigation of the binding characteristics of ß-amyloid fibrils.

Timely and accurate diagnosis of Alzheimer's disease (AD) remains a major challenge in the medical arena. ß-amyloid (Aß) imaging techniques such as positron emission tomography and single photon emission computed tomography require the use of an imaging probe. To date, only flutemetamol, florbetaben and florbetapir have been approved for clinical use as imaging probes. Design of imaging probes requires a detailed understanding of disease mechanism(s) and receptor-ligand interaction. In this study, molecular docking, molecular dynamics and binding free energies were used to investigate the multiple binding sites exhibited by ß-amyloid fibrils. Protein atomic models 2BEG, 5KK3, 2M4J, 2LMN, 5OQV, 2NAO, 2MVX and 2MXU (protein databank codes) were used to investigate the nature and location of binding sites and binding profiles of selected molecules with known affinities. Although amyloid fibrils are known to have multiple binding sites, we demonstrated that model 2MXU possesses one site which is druggable and can bind with common scaffolds currently being used in the imaging of amyloid fibrils. Models 2NAO, 5KK3 and 2M4J revealed that even though multiple sites may be available in some fibrils, the entire protein may not have a druggable site. Molecular dynamics revealed atomic models 2MXU and 2MVX to be the least flexible among the list. The outcomes of this investigation can be translated to assist in designing novel molecules that can be used for brain imaging in Alzheimer's disease.

High-Throughput 2D Heteroatom Graphene Bioelectronic Nanosculpture: A Combined Experimental and Theoretical Study.

In this study, chemical vapor deposition-synthesized heteroatom graphene (HGr) bioelectronic interfaces have been developed for ultrafast, all-electronic detection and analysis of molecules by driving them through tiny holes-or atompores-in a thin lattice of the graphene sheet, including the efforts toward facilitating enhanced electrocatalytic and mapping electron transport activities. The presence of chlorine, nitrogen, and oxygen in the crystalline graphitic layers (<7) has been confirmed using Raman spectroscopy, X-ray photoelectron spectroscopy, and high-resolution transmission electron microscopy. We report a swift bioelectrocatalytic response to step-by-step additions of the substrate with the achievement of a steady current within a few seconds. The response limit was 2.07 µM with a dynamic range of sensing from 2.07 µM to 2.97 mM. The electronic properties and adsorption energies of hydroquinone and p-benzophenone molecule adsorption on pristine, O-, N-, and Cl-doped graphene nanosheet surfaces were systematically investigated using first-principles calculations. The results revealed that the adsorption capacity was improved upon doping graphene nanosheets with O, N, and Cl atoms. Hence, Cl-doped graphene nanosheets were shown as a promising adsorbent toward hydroquinone and p-benzophenone detection.

The effects of two-dimensional TiSe2 on the thermoelectric, electronic and optical response of Yb14MnSb11/AlSb9Yb11 heterostructures - A theoretical study.

Two-dimensional TiSe2, with Yb14MnSb11 and AlSb9Yb11 thermoelectric materials, were used to generate heterostructures. The electronic and optical calculations were done using the Materials Studio 2018 modelling software package, employing the Cambridge Serial Total Energy Package code and using the generalised gradient approximation with Perdew-Burke-Ernzerhof exchange-correlation functionals. However, the electronic results obtained revealed a reduction in the calculated band gap and an increase in the slope of the density of state at the Femi level, as well as the energy bands of the generated heterostructures was reported. Partial density of states showed that various orbitals were present in the thermoelectric materials. The thermal transport and electronic properties are compared using the Boltzmann transport theory and Mott derived equations, which were expressed in the maximum attainable figure of merit. A variation in the electric potential of the layers is observed. The dielectric function is found to decrease in both thermoelectric layers generated and far more than the Yb14MnSb11-TiSe2 layer, which was more negative. The reduction in reflectivity of AlSb9Yb11TiSe2 layer and elevation of the Yb14MnSb11-TiSe2 layer is observed. Upon forming heterostructures with TiSe2, the conductivity reduced in the high frequency, due to the generated complex multicomponent compounds.