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In this work, silver-entecavir nanoparticles (Ag-ETR) were successfully synthesized using the green synthetic procedure and caped by entecavir that worked as a reducing agent, as it has amino and hydroxy functional groups. Synthesis of NPs was confirmed by UVS spectrophotometry and thin-layer chromatography while surface functionalization was studied using Fourier transform infrared spectrometer and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS). Morphological studies of synthesized NPs were performed using the scanning electron microscopy, atomic force microscopy, and zetasizer. Structure of self-assembly Ag-ETR nano-clusters was proposed by UV–vis spectroscopy, FT-IR, H-NMR, X-ray diffraction, and SEM-EDS. The stoichiometry of Ag-ETR NPs was found to be 8:2 (ETR and Ag) and 120–188 nm in size, while having a surface charge –13.7 mv. Decomposition kinetics of Ag-ETR NPs was determined by Horowitz-Metzger method and allied kinetic parameter including Gibb’s free energy (ΔG), change in entropy (ΔS) and heat of enthalpy (ΔH) were determined. ETR conjugated Ag NPs exhibited significantly increased stability and aqueous solubility. Ag-ETR NPs could be a promising agent to have better synergistic effect, are expectedly reduce drug resistance which is corroborated to different cellular uptake mechanisms and may increase bioavailability as NPs had high water solubility.

The non-H atoms of the title molecule, C6H4BrNO2, are essentially coplanar with an r.m.s. deviation of 0.040 Å. In the crystal, π–π stacking occurs between parallel benzene rings of adjacent molecules with centroid–centroid distances of 3.643 (3) and 3.741 (3) Å. Weak intermolecular C—H...O hydrogen bonding and short Br...O contacts [3.227 (4) 3.401 (4) Å] are also observed in the crystal structure. The crystal studied was a non-morohedral twin with a 26.1 (6)% minor component.

There are one-and-a-half independent molecules in the asymmetric unit of the title compound, C18H20N2O4. One molecule is centrosymmetric with the mid-point of the N—N bond located on a center of inversion. In the other, which lies on a general position, the benzene rings are aligned at 21.6 (1)°. Weak intermolecular C—H...O hydrogen bonding is present in the crystal strcture.

The molecule of the title compound, C19H14Cl2O2, has two benzene rings connected to a methylene C atom, and the rings are aligned at 66.3 (1)°. Intermolecular C—H...π and π–π stacking interactions are observed in the crystal structure, the centroid–centroid distances between parallel benzene rings being 3.7529 (12) and 3.6201 (12) Å, respectively.

In the title molecule, C12H15NO5, the nitrophenoxy portion is approximately planar (r.m.s. deviation = 0.034 Å) and makes an angle of 84.8 (1)° with respect to the –CH2–C(=O)–O–C fragment. In the crystal, π–π stacking is observed between nearly parallel benzene rings of adjacent molecules, the centroid–centroid distance being 3.6806 (10) Å. Weak intermolecular C—H...O hydrogen bonding is present in the crystal structure.

In the title compound, C33H36O6, two naphthalene ring systems are connected through a methylene linkage [C—C—C = 114.9 (2)°]; the ring systems are aligned at an angle of 76.5 (1)°. Of the two –O–CH2–C(=O)–C(CH3)3 substituents, one adopts an extended conformation whereas the other is U-shaped. In the crystal, molecules are linked via weak C—H...O hydrogen bonding, forming supramolecular chains running along the c axis.

The cyclohexene ring in the title compound, C29H33Cl2NO10S2, adopts an envelope conformation, with the C atom bearing the two methyl groups representing the flap. This atom deviates by 0.63 (1) Å from the plane through the other five ring atoms (r.m.s. deviation = 0.11 Å). The molecular conformation is stabilized by an intramolecular N—H...S hydrogen bond. The crystal studied was a non-merohedral twin, with a minor twin component of 29%.

Methanolic extracts of different parts of five medicinal plants, Ferula assafoetidaL. resin, Grewia asiaticaL. leaves, Ipomoea hederaceaJacq. seeds, Lepidium sativumL. seeds and Terminalia chebulaRetz. fruits were tested in vitrofor their cytotoxic, phytotoxic, insecticidal, nematicidal and anthelmintic activities. Ipomoea hederaceashowed very significant phytotoxic and cytotoxic activity, with 100% inhibition of Lemna minorgrowth and 100% death of Artemia salinaat concentrations of 1000 and 100 µg mL-1. Grewia asiaticaexhibited very weak activities while Lepidium sativumand Ferula assafoetidashowed moderate to good potential in all three bioassays. The results suggest screening of Ipomoea hederaceaseeds further for isolation of bioactive compounds that may be responsible for its toxic potential.

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis ( p  < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication ( p  < 0.05, p  < 0.01, and p  < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Currently, chemotherapy is one of the most practiced approaches for the treatment of cancers. However, existing chemotherapeutic drugs have poor aqueous solubility, poor selectivity, higher systematic toxicity, and poor target accumulation. In this study, we designed and synthesized a boronic acid/ester-based pH-responsive nano-valve that specifically targets the microenvironment in cancer cells. The nano-valve comprises phenylboronic acid-coated mesoporous silica nanoparticles (B-MSN) loaded with polyphenolic compound Rosmarinic acid (ROS-B-MSN). The nano-valve was further coated with lignin (LIG) to achieve our desired LIG-ROS-BMSN nano-valve for targeted chemotherapy against Hep-G2 and NCI-H460 cell lines. The structure and properties of NPs were characterized by Fourier-transformed infrared spectroscopy (FTIR), Scanning Electron Microscopy (SEM) in combination with EDX, and Dynamic light scattering (DLS). The outcomes revealed that the designed LIG-ROS-BMSN were in the nanorange (144.1 ± 0.70 nm), had negative Zeta potential (-15.7 ± 0.46 mV) and had a nearly spherical morphology. In vitro , drug release investigations showed a controlled pH-dependent release profile under mild acidic conditions that could enhance the targeted chemotherapeutic response against cancer in mild acidic environments. The obtained LIG-ROS-BMSN nano valve achieved significantly lower IC 50 values of (1.70 ± 0.01 μg/mL and 3.25 ± 0.14 μg/mL) against Hep-G2 and NCI-H460 cell lines as compared to ROS alone, which was (14.0 ± 0.7 μg/mL and 29.10 ± 0.25 μg/mL), respectively. The cellular morphology before and after treatment was further confirmed via inverted microscopy. The outcomes of the current study imply that our designed LIG-ROS-BMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Dental implants are commonly used for tooth replacement tools due to their good oral rehabilitation and reconstruction capacities. Dental implants treatment for natural teeth is desired to achieve successful implants treatment with improved osseointegration through promotion of mammalian cell activity and prevention of bacterial activity. Honey is potentially known for its antimicrobial and antibacterial potential, specifically for burns and wound healing. In this study, honey based silver nanoparticles were synthesized using various concentrations of honey. The synthesized HNY-AgNPs, MSN and HNY-AgMSN were characterized for their surface Plasmon resonance using UV spectroscopy, Hydrodynamic diameter using Zetasizer. Morphology using AFM. Furthermore, surface functional groups were characterized using FTIR spectroscopy at 4cm-1 resolutions. The developed hybrid nanoparticles were tested for their anti-bacterial activity at concentration of 3000µg/mL. It was found HNY-AgNPs was active against both bacterial strains i.e, Streptococcus mutans and streptococcus aureus. HNY-AgNPs-MSN hybrid implant demonstrated potential new type of dental implants, which can offer an effective design for the fabrication of advanced dental implants.

The biofilm formation is still prevalent mechanism of developing the drug resistance in the Pseudomonas aeruginosa , gram-negative bacteria, known for its major role in nosocomial, ventilator-associated pneumonia (VAP), lung infections and catheter-associated urinary tract infections. As best of our knowledge, current study first time reports the most potent inhibitors of LasR, a transcriptional activator of biofilm and virulence regulating genes in, Pseudomonas aeruginosa LasR, utilizing newly functionalized imidazoles (5a-d), synthesized via 1,3-dipolar cycloaddition using click approach. The synthesized ligands were characterized through Mass Spectrometry and 1H NMR. The binding potency and mode of biding of ligands. Quantum Mechanical(QM) methods were utilized to investigate the electronic basis, HOMO/LUMO and dipole moment of the geometry of the ligands for their binding potency. Dynamics cross correlation matrix (DCCMs) and protein surface analysis were further utilized to explore the structural dynamics of the protein. Free energy of binding of ligands and protein were further estimated using Molecular Mechanical Energies with the Poisson-Boltzmann surface area (MMPBSA) method. Molecular Docking studies revealed significant negative binding energies (5a - 10.33, 5b -10.09, 5c - 10.11, and 5d -8.33 KJ/mol). HOMO/LUMO and potential energy surface map estimation showed the ligands(5a) with lower energy gaps and larger dipole moments had relatively larger binding potency. The significant change in the structural dynamics of LasR protein due to complex formation with newlyfunctionalized imidazoles ligands. Hydrogen bond surface analysis followed by MMPBSA calculations of free energy of binding further complemented the Molecular docking revelations showing the specifically ligand (5a) having the relatively higher energy of binding(-65.22kj/mol).Communicated by Ramaswamy H. Sarma.

Herein, we describe the fabrication of green bell pepper, Capsicum annuum L. extract capped gold nanoparticles (CA-AuNPs) in aqueous medium using tetrachloroaurate (HAuCl 4 ·3H 2 O) as precursor salt and sodium hydroxide (NaOH) solution as accelerator as well as pH adjuster. Formation of CA-AuNPs was verified via colour change from yellowish to ruby red with further confirmation through surface plasmon resonance (SPR) band at 519 nm using ultraviolet violet-visible (UV-Vis) spectroscopy. Other characterizations techniques include, Fourier transform infra-red (FTIR) spectroscopy, atomic force microscopy (AFM), dynamic light scattering (DLS) with Zeta-potential analysis (ZPA) and X-ray diffraction (XRD) method. The resulting AuNPs were efficaciously implemented as highly sensitive colorimetric sensor for selective detection of Fe 2+ in the presence of several interfering cations including Fe 3+ . Importantly, the fabricated CA-AuNPs based colorimetric sensor functioned linearly in the range of 0.3-7.0 ppb Fe 2+ , based on increasing absorption intensity with R 2 value of 0.9938 using UV-Vis spectrometry. The limit of detection (LOD) and limit of quantification (LOQ) for Fe 2+ were estimated as 0.036 and 0.12 ppb, respectively. Finally, the sensor was effectively tested for determination of Fe 2+ in some locally collected real water samples., Competing Interests: Declaration of competing interest The authors declare no financial interests or personal relationship to influence the work reported in this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Naegleria fowleri ( N. fowleri ) causes primary amoebic meningoencephalitis (PAM) which almost always results in death. N. fowleri is also known as "brain-eating amoeba" due to its literal infestation of the brain leading to an inflammatory response in the brain tissues. Currently, there is no single drug that is available to treat PAM, and most treatments are combinations of antifungal, anticancer, and anti-inflammatory drugs. Recently nanotechnology has gained attention in chemotherapeutic research converging on drug delivery, while oleic acid (OA) has shown positive effects on the human immune system and inflammatory processes. In continuation of our recent research in which we reported the effects of oleic acid conjugated with silver nanoparticles (OA-AgNPs) against free-living amoeba Acanthamoeba castellanii , in this report, we show their antiamoebic effects against N. fowleri . OA alone and its nanoconjugates were tested against the amoeba by using amoebicidal and host cell cytopathogenicity assays. Trypan blue exclusion assay was used to determine cell viability. The results revealed that OA-AgNPs exhibited significantly enhanced antiamoebic effects ( P < 0.05) against N. fowleri as compared to OA alone. Evidently, lactate dehydrogenase release shows reduced N. fowleri -mediated host cell cytotoxicity. Based on our study, we anticipate that further studies on OA-AgNPs could potentially provide an alternative treatment of PAM.

Numerous nanotechnological approaches have been widely practiced to improve the bioavailability of less aqueous soluble drugs; phospholipid based vesicles (liposomes) being the most widely applied drug delivery system. However; due to stability issues, large scale production limitations, sterilization and long term storage problems; non-ionic surfactant based vesicles (niosomes) are considered their excellent counterparts. Niosomes are vesicles of non-ionic surfactants having the ability to carrying both hydrophilic and hydrophobic drugs in their inner aqueous or lipid bilayer compartments. In this research work, triazole based non-ionic surfactant (TBNIS) was synthesized and characterized by different spectroscopic techniques and then screened for biocompatibility using NIH 3T3 cell line, blood hemolysis assay and acute toxicity in mice. The synthesized surfactant was then checked for niosomes' formation, Amphotericin B loading and entrapment efficiency, drug release, stability and bioavailability of the drug was assessed and compared with free drug solution. The synthesized surfactant was found biocompatible and caused less blood hemolysis, greater cell vial ability and negligible toxicity in animals. The size of drug loaded niosomal vesicles of TBNIS based surfactant was 179.9 ± 3.23 nm with smaller size distribution i.e. 0.29 ± 0.02. The triazole based surfactant vesicles showed 88.76 ± 3.45 % drug entrapment efficiency, sustained drug release profile and stability. The drug in TBNIS based vesicles has greater oral bioavailability 0.099 ± 0.03 as compared to plan drug solution 0.012 ± 0.023 μg/mL. Results of this study suggests that the newly synthesized triazole based surfactant can be used in drug delivery for improving bioavailability of less water soluble drugs like Amphotericin B., Competing Interests: Declaration of Competing Interest All the authors of this manuscript declare that there is no conflict of interest, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii . Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.

Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii ( p ＜ 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.

Central nervous system (CNS) infections caused by free-living amoebae such as Acanthamoeba species and Naegleria fowleri are rare but fatal. A major challenge in the treatment against the infections caused by these amoebae is the discovery of novel compounds that can effectively cross the blood-brain barrier to penetrate the CNS. It is logical to test clinically approved drugs against CNS diseases for their potential antiamoebic effects since they are known for effective blood-brain barrier penetration and affect eukaryotic cell targets. The antiamoebic effects of clinically available drugs for seizures targeting gamma-amino butyric acid (GABA) receptor and ion channels were tested against Acanthamoeba castellanii belonging to the T4 genotype and N. fowleri. Three such drugs, namely, diazepam (Valium), phenobarbitone (Luminal), phenytoin (Dilantin), and their silver nanoparticles (AgNPs) were evaluated against both trophozoites and cysts stage. Drugs alone and drug conjugated silver nanoparticles were tested for amoebicidal, cysticidal, and host-cell cytotoxicity assays. Nanoparticles were synthesized by sodium borohydride reduction of silver nitrate with drugs as capping agents. Drug conjugated nanoconjugates were characterized by ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopies and atomic force microscopy (AFM). In vitro moebicidal assay showed potent amoebicidal effects for diazepam, phenobarbitone, and phenytoin-conjugated AgNPs as compared to drugs alone against A. castellanii and N. fowleri. Furthermore, both drugs and drug conjugated AgNPs showed compelling cysticidal effects. Drugs conjugations with silver nanoparticles enhanced their antiacanthamoebic activity. Interestingly, amoeba-mediated host-cell cytotoxicity was also significantly reduced by drugs alone as well as their nanoconjugates. Since, these drugs are being used to target CNS diseases, their evaluation against brain-eating amoebae seems feasible due to advantages such as permeability of the blood-brain barrier, established pharmacokinetics and dynamics, and United States Food and Drug Administration (FDA) approval. Given the limited availability of effective drugs against brain-eating amoebae, the clinically available drugs tested here present potential for further in vivo studies.