Comparative study of the efficiency of silicon carbide, boron nitride and carbon nanotube to deliver cancerous drug, azacitidine: A DFT study.

Herein we have made a comparative study of the efficiency of three different nanotubes viz. Carbon nanotube (CNT), boron nitride nanotube (BNNT) and silicon carbide nanotube (SiCNT) to deliver the cancerous drug, Azacitidine (AZD). The atomistic description of the encapsulation process of AZD in these nanotubes has been analyzed by evaluating parameters like adsorption energy, electrostatic potential map, reduced density gradient (RDG). Higher adsorption energy of AZD with BNNT (-0.66eV), SiCNT (-0.92eV) compared to CNT (-0.56eV) confirms stronger binding affinity of the drug for the former than the later. Charge density and electrostatic potential map suggest that charge separation involving BNNT and CNT is more prominent than SiCNT. Evaluation of different thermodynamic parameters like Gibbs free energy, enthalpy change revealed that the overall encapsulation process is spontaneous and exothermic in nature and much favorable with BNNT and SiCNT. Stabilizing interactions of the drug with BNNT and SiCNT has been confirmed from RDG analysis. ADMP molecular dynamics simulation supports that the encapsulation process of the drug within the NT at room temperature. These results open up unlimited opportunities for the applications of these NTs as a drug delivery system in the field of nanomedicine.

pH-regulated hydrothermal synthesis and characterization of Sb4O5X2 (X = Br/Cl) and its use for the dye degradation of methyl orange both with and without light illumination.

A pH-regulated hydrothermal synthesis method was employed to synthesize Sb4O5Br2 and Sb4O5Cl2 crystallites. Characterization is done by single crystal X-ray diffraction, powder X-ray diffraction, infra-red spectroscopy, scanning electron microscopy and DFT studies. The compounds crystallize in monoclinic symmetry with a P21/c space group. Complete structural analysis of the Sb4O5Br2 compound by using single crystal X-ray diffraction data is performed for the first time and a comparative study with Sb4O5Cl2 is also discussed. The SEM study reveals that the surface morphology changes with the variation of pH for bromide compounds, whereas pH change does not affect the morphology of the chloride analogues. Electronic band structures of the synthesized oxyhalides were investigated in order to understand their catalytic effects in the dye degradation reactions in dark as well as sunlight conditions.

Inhibitory effect of compounds extracted from Monochoria hastata (L.) Solms on SARS-CoV-2 main protease: An insight from molecular docking and MD-simulation studies.

Using molecular docking and other studies, 20 compounds extracted from Monochoria hastata (L.) Solms were screened, and their inhibitory efficiency examined against main protease (3CLpro) of SARS CoV-2. All the compounds were found to binding with 3CLpro through van der Waals and electrostatic forces of attractions. Among them, Azelaic dihydrazide (ADZ) was found to have the highest docking score. 3CLpro-ADZ complex was studied by MD simulation. ADZ was found to disrupt the structure of 3CLpro after 2 ns. RMSD and RMSF analysis along with sequence and binding energy analysis suggest that ADZ can be a potential drug against SARS CoV-2.

Critical Antileishmanial in vitro Effects of Highly Examined Gold Nanoparticles.

INTRODUCTION: The current therapeutic armory for visceral leishmaniasis (VL) caused by Leishmania donovani complex is inadequate, coupled with serious limitations. Combination therapy has proved ineffective due to mounting resistance; however, the search for safe and effective drugs is desirable, in the absence of any vaccine. There is a growing interest in the application of nanoparticles for the therapeutic effectiveness of leishmaniasis. Aimed in this direction, we assessed the antileishmanial effect of gold nanoparticles (GNP) against L. donovani in vitro. METHODS: GNP were synthesized and characterized for particle size by dynamic light scattering (DLS) and atomic force microscopy (AFM) and for optical properties by UV-visible spectroscopy. Cytotoxicity of GNP was measured by the MTT proliferation assay. The antileishmanial activity of the nanoparticles was evaluated against L. donovani promastigotes and macrophage-infected amastigotes in vitro. RESULTS: GNP showed a strong SPR peak at 520 nm and mean particle size, polydispersity index (PDI), and zeta potential of 56.0 ± 10 nm, 0.3 ± 0.1 and -27.0 ± 3 mV, respectively. The GNPs were smooth and spherical with a mean particle diameter of 20 ± 5 nm. Nanoparticles [1.2-100 µM] did not reveal any cytotoxicity on RAW 264.7 murine macrophage cell line, but exerted significant activity against both promastigotes and amastigote stages of L. donovani with 50% inhibitory concentrations (IC50) of 18.4 ± 0.4 µM and 5.0 ± 0.3 µM, respectively. GNP showed significant antileishmanial activity with deformed morphology of parasites and the least number of surviving promastigotes after growth reversibility analysis. CONCLUSION: GNP may provide a platform to conjugate antileishmanial drugs onto the surface of nanoparticles to enhance their therapeutic effectiveness against VL. Further work is warranted, involving more in-depth mechanistic studies and in vivo investigations.

Inhibitory capacity of chloroquine against SARS-COV-2 by effective binding with angiotensin converting enzyme-2 receptor: An insight from molecular docking and MD-simulation studies.

The main binding site for SARS-COV-2 spike protein in human body is human Angiotensin converting enzyme 2 (ACE2) protein receptor. Herein we present the effect of chloroquine (CLQ) on human ACE2 receptor. Molecular docking studies showed that chloroquine have a docking score is quite high compare to other well known drugs. Furthermore, molecular dynamics (MD) studies with CLQ docked ACE2 results in large fluctuations on RMSD up to 2.3 ns, indicating conformational and rotational changes due to the presence of drug molecule in the ACE2 moiety. Analysis of results showed that CLQ can effect the conformation of human ACE2 receptor. We believed that this work will help researchers to understand better the effect of CLQ on ACE2.

Environmentally hazardous gas sensing ability of MoS2-nanotubes: an insight from the electronic structure and transport properties.

Herein we have investigated the ability of the (6,6) MoS2-nanotube (NT) to sense environmentally hazardous electrophilic and nucleophilic gases using density functional theory (DFT). CO, CO2, H2O and NH3 gases were chosen for adsorption on the (6,6) MoS2-NT and different adsorption parameters such as adsorption energy, projected density of states (PDOS), band structure and structural changes after adsorption were evaluated. Nucleophilic gases NH3 and H2O showed a fairly high amount of electron density transfer from gas molecules to the NT while the opposite trend was realized for electrophilic gases CO and CO2. Among the four gases, H2O has the highest amount of adsorption energy (-1.74 eV) and a moderately high amount of charge transfer from H2O to the NT. Gas sensing behaviour was further rationalized from the enhanced I-V characteristics of gas adsorbed nanotubes compared to pristine ones. Analysis of results revealed that the (6,6) MoS2-NT showed a decent level of gas sensing properties towards CO, CO2, H2O and NH3 gases, and high selectivity for H2O makes the MoS2-NT superior to previously reported MoS2-monolayer in this matter. These results suggest the possibility of fabrication of highly efficient MoS2-NT based gas sensors for environmentally hazardous gases.

Screening of potential drug from Azadirachta Indica (Neem) extracts for SARS-CoV-2: An insight from molecular docking and MD-simulation studies.

Azadirachta Indica (Neem) extracts have been known for their anti-bacterial and other effects since ancient times. The present work examines the inhibitory activity of Neem extracts on Papain like protease (PLpro) of the novel coronavirus SARS-CoV-2. The activity is analysed by molecular docking study along with molecular dynamics simulation. All the studied Neem compounds showed decent level of inhibitory activity against PLpro of SARS-CoV-2. Among them, desacetylgedunin (DCG) found in Neem seed showed the highest binding affinity towards PLpro. Furthermore, MD-simulation studies supported by standard analysis (e.g. root mean square deviation and fluctuation (RMSD, RMSF), radius of gyration, solvent accessible surface area (SASA)) showed large impact on the structure of PLpro by DCG. We believe that the significant effect of DCG on PLpro may help in therapeutic efforts against SARS-CoV-2.

Inhibitory activity of hydroxychloroquine on COVID-19 main protease: An insight from MD-simulation studies.

The present work is an investigation to test hydroxychloroquine as an inhibitor for the COVID-19 main protease. Molecular docking studies revealed a high docking score and interaction energies and decent level of docking within the cavity in protease moiety. Molecular dynamics simulations also lead to the evaluation of conformational energies, average H-bonding distance, RMSD plots etc. Large RMSD fluctuations for the first 2 ns seem to provide the conformational and rotational changes associated with the drug molecule when it comes into the vicinity on the protease matrix. Snapshots of structural changes with respect to time vividly indicates that drug molecule has a profound impact on the binding sites as well as overall geometry of the protease moiety. On the whole, hydroxyxhloroquine confers good inhibitory response to COVID-19 main protease. We hope the present study should help workers in the field to develop potential vaccines and therapeutics against the novel coronavirus.

Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis.

Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL. Nanoliposomal artemisinin (NLA) was prepared by thin-film hydration method and optimized using Box-Behnken design with a mean particle diameter of 83±16 nm, polydispersity index of 0.2±0.03, zeta potential of -27.4±5.7 mV, and drug loading of 33.2%±2.1%. Morphological study of these nanoliposomes by microscopy showed a smooth and spherical surface. The mechanism of release of artemisinin from the liposomes followed the Higuchi model in vitro. NLA was free from concomitant signs of toxicity, both ex vivo in murine macrophages and in vivo in healthy BALB/c mice. NLA significantly denigrated the intracellular infection of Leishmania donovani amastigotes and the number of infected macrophages ex vivo with an IC50 of 6.0±1.4 µg/mL and 5.1±0.9 µg/mL, respectively. Following treatment in a murine model of VL, NLA demonstrated superior efficacy compared to artemisinin with a percentage inhibition of 82.4%±3.8% in the liver and 77.6%±5.5% in spleen at the highest dose of 20 mg/kg body weight with modulation of cell-mediated immunity towards protective Th1 type. This study is the first report on the use of a liposomal drug delivery system for artemisinin as a promising alternative intervention against VL.

Excellent catalytic activity of magnetically recoverable Fe3O4-graphene oxide nanocomposites prepared by a simple method.

An Fe3O4-graphene oxide nanocomposite has been synthesized via a chemical reaction with a magnetite particle size of 18-25 nm. The resulting nanocomposite can be easily manipulated by an external magnetic field, exhibits excellent catalytic activity and may be reused for several cycles with marginal loss of activity. This recyclable nanocomposite provides an efficient, economic, novel route for multi-component A(3) coupling reactions of aldehydes, amines and alkynes and gives the propargylamine in excellent yields.

O-tert-butyldiphenylsilyl coumarin and dicoumarol: a case toward selective sensing of F- ions in organic and aqueous environments.

O-tert-Butyldiphenylsilyl coumarin 1 and 2 dicoumarol have been synthesized and their anion binding properties have been examined in organic and aqueous organic solvents. Compound 1 senses F(-) selectively over the other anions examined in CHCl3 by exhibiting a greater increase in emission. In contrast, compound 2 shows similar selectivity in CHCl3 giving ratiometric change in emission as well as color. In addition, both 1 and 2 are capable of detecting F(-) in water ensuing the cleavage of Si-O bonds. They also show cell permeability and demonstrate their abilities to detect F(-) in a living system.

Surface tunability of nanoparticles in modulating platelet functions.

Metallic nanoparticles are attractive candidates as MRI contrast agents and mediators for drug delivery, diagnostics, and therapy. Direct contact and exposure to blood circulation is common in many such applications. The consequent thrombotic response may therefore be important to study. The main objective of the present work was to study how platelet functions were changed in the presence of different nano-surface or surface capping, which may provide a measure for the safety of a nanoparticle, and also assess the use of such nanoparticles in platelet modulation. Aggregometry, ATP release reaction, flow cytometry and immune-blotting studies were performed to study platelet response to different nano-particles (iron oxide, gold and silver). For each nanoparticle surface conjugation (capping) was varied. It was found that citric acid functionalized iron oxide nanoparticles have anti-platelet activity, with a decrease in aggregation, tyrosine phosphorylation level, and granule release. On the other hand in other cases (e.g. gold nanoparticles) pro-aggregatory response was observed in the presence of nanoparticles and, in some cases, the nanoparticles behaved neutrally (e.g. for starch-coated iron oxide nanoparticles). Therefore, nanoparticles can induce antiplatelet or a pro-aggregatory response, or remain neutral depending on surface capping. A related observation is that antiplatelet drugs can be made more potent by nanoparticle conjugation.

Anthracene appended pyridinium amide-urea conjugate in selective fluorometric sensing of L-N-acetylvaline salt.

A new anthracene labeled pyridinium amide-urea conjugate 1 has been designed and synthesized. The receptor shows a different fluorometric response with L-N-acetylvaline and L-N-acetylalanine salts in CH3CN in contrast to the other salts of L-N-acetyl α-amino acids and (S)-α-hydroxy acids studied. Upon complexation of the tetrabutylammonium salt of L-N-acetylvaline, the emission of 1 increases accompanied by the formation of a new band at higher wavelength and this characteristic change distinguishes it from other anionic substrates studied. The binding interaction has been studied by ¹H NMR, fluorescence and UV titration experiments.

Quinoline based receptor in fluorometric discrimination of carboxylic acids.

Quinoline and naphthalene-based fluororeceptors 1 and 2 have been designed and synthesized for detection of hydroxy carboxylic acids in less polar solvents. The receptor 1 shows monomer emission quenching followed by excimer emission upon hydrogen bond-mediated complexation of carboxylic acids. The excimer emission distinguishes aromatic dicarboxylic acids from aliphatic dicarboxylic acids and even long chain aliphatic dicarboxylic acids from short chain aliphatic dicarboxylic acids. The receptor 1 is found to be selective for citric acid with a strong excimer emission in CHCl(3). On the contrary, the receptor 2 exhibited less binding constant value and did not form any excimer upon complexation with the same acids under similar conditions. This established the role of quinoline ring nitrogen in binding with the acids.