Highest Inhibitory Effect Research Articles

Fabrication of an antibacterial hydrocolloid dressing for the management of wound infection caused by antibiotic-resistant bacteria: In Vitro study

The purpose of this study was to fabricate an antibacterial hydrocolloid dressing for the management of infected wounds with multidrug-resistant (MDR) bacteria. Among hospitalized patients, infections caused by MDR bacteria are a major cause of morbidity and mortality, especially in burn units. A hydrocolloid dressing was fabricated using pectin, gelatin, and sodium carboxymethyl cellulose as well as 16, 32, and 64 mg/ml of CM11 antibacterial peptide. After the characterization of the hydrocolloid dressing, its antibacterial activity against MDR strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli was investigated. The optimal cross-linking duration using glutaraldehyde vapor was three hours, resulting in a degradation of 28 % after 48 hours. SEM showed the uniform structure of the fabricated dressings. The Young's modulus, tensile strength, and elongation at break were 19 kPa, 0.041 MPa, and 180 %, respectively. The water absorption and water vapor transmission rates were 149 % and 464 g/m2/day. The peptide release assay showed that more than 25 % of the peptide was released during 24 hours. The antibacterial activity of the hydrocolloid was dose-dependent, with the highest inhibitory effect at a concentration of 64 µg/ml. Based on the time-killing assay, the peptide in a dose-dependent manner caused a decrease in CFU of the three bacteria after the first 6 hours compared to the control (without treatment) and the dressing without peptide (p ≤ 0.05). However, at a concentration of 64 µg/ml, this reduction was present for up to 24 hours. The results showed that the antibacterial hydrocolloid dressing can be considered as a wound dressing candidate to deal with wound infections.

Instant and Synergistic Antibacterial Coating of Silver Loaded With Silica Nanoparticles for Different Applications

ABSTRACTThe synthesis of antibacterial nanoparticles is one of the most promising strategies to get rid of the primary threat that pathogenic bacteria pose to public health. Silver nanoparticles (AgNPs) are a promising antibacterial agent with robust and broad antibacterial characteristics that have the potential to resolve this issue. A straightforward reduction–impregnation approach for creating an Ag‐loaded SiO2 nanocomposite has been presented in the present study. First, the well‐known Stöber method was employed to produce silica nanoparticles, which were subsequently examined utilizing an X‐ray diffraction (XRD), a field emission scanning electron microscope (FE‐SEM), and a high‐resolution transmission electron microscope (HR‐TEM). After that, a composite made of Ag@SiO2 was produced and examined. AgNPs, which are loaded with silica and exhibit instantaneous and synergistic antibacterial activity against Gram‐positive “Bacillus subtilis” (B. subtilis) bacteria, were demonstrated. The coating layer that was produced also showed strong adherence to the steel substrate, a high inhibitory effect against the (B. subtilis), and versatility in its application across various sectors.

A new herbal extract carbon nanodot nanomedicine for anti-renal cell carcinoma through the PI3K/AKT signaling pathway.

New Re carbon nanodots with narrow size distribution, good water solubility and high cell membrane permeability were prepared from a herbal extract. They exhibited high inhibitory effects on renal cancer A498 cells and renal cell carcinoma. They could stimulate the production of ROS, induce mitochondrial dysfunction, and accelerate the release of intracellular calcium ions in the A498 cells. Transcriptomic tests were performed on A498 cells after administration, and the results were analyzed by qPCR and immunofluorescence. The results suggested that the Re carbon nanodots could downregulate the abnormally activated PI3K/AKT signaling pathway and perform cell cycle arrest in the S phase along with the inhibition of cell proliferation. Finally, in conjunction with the abnormal mitochondrial function, the Re carbon nanodots could ultimately promote the apoptosis of the A498 cells. In vivo tumor-bearing mouse experiments further showed that the Re carbon nanodots had a strong inhibitory effect on xenograft kidney cancer tumors. The prepared Re carbon nanodots have good anti-renal cancer A498 cell and renal cell carcinoma bioactivity and are expected to be a potential drug for the treatment of kidney cancer with low toxicity and high safety.

Assessment of the bioactivities of spray-dried pure and Zn-containing bioactive glass by experimental and DFT analysis

The bioactive glass contains CaO, SiO2, and P2O5 in proportion and is applied in bone tissue engineering, plastic surgery, and dentistry because of its excellent bioactivity, biocompatibility, and osteoconductivity. Doping metal ions into a bioactive glass is an efficient way to enhance its functionality and medical applicability. Zn ions have been proven to have a high inhibitory effect on bacterial growth, so Zn-containing bioactive glass has attracted much attention. The literature presents conflicting findings on whether Zn dopants enhance or deteriorate the bioactivity of bioactive glass, and there is no clear answer. To clarify the role of Zn ions on the bioactivity of bioactive glass, pure and Zn-containing bioactive glass samples were synthesized using a spray drying technique followed by in vitro immersion. XPS and theoretical calculations showed that Zn dopants decreased non-bridging oxygen concentration in bioglass. XRD, SEM, and FTIR demonstrated that the Zn dopants decreased bioglass activity. The dissolution study indicated that Zn dopants strongly bond to the non-bridging oxygen near the Ca ion in bioglass, decreasing its bioactivity.

A Multifunctional Low-Temperature Photothermal Nanomedicine for Melanoma Treatment via the Oxidative Stress Pathway Therapy.

Melanoma is a highly aggressive and dangerous malignant skin tumor and there is an urgent need to develop effective therapeutic approaches against melanoma. The main objective of this study was to construct a multifunctional nanomedicine (GNR@PEG-Qu) to investigate its therapeutic effect on melanoma from the oxidative stress pathway. First, the nanomedicine GNR@PEG-Qu was synthesized and characterized, and its photothermal and antioxidant properties were confirmed. In addition, in vivo imaging capabilities were observed. Finally, the tumor inhibitory effects of GNR@PEG-Qu in vivo and in vitro as well as its biosafety were observed. GNR@PEG-Qu shows good photothermal and anti-oxidation properties. Following exposure to 1064 nm laser irradiation in the second near-infrared II (NIR-II) window, GNR@PEG-Qu shows anti-tumor ability through low-temperature photothermal therapy (PTT) adjuvant drug chemotherapy. GNR@PEG-Qu makes full use of the antioxidant capacity of quercetin, reduces ROS levels in melanoma, alleviates oxidative stress state, and achieves "oxidative stress avoidance" at the tumor site. Quercetin can also downregulate the expression of the heat shock protein Hsp70, which will improve the thermal sensitivity of the tumor site and enhance the efficacy of low-temperature PTT. GNR@PEG-Qu nanoagent exhibits synergistic treatment and high tumor inhibition effects, which is a promising strategy developed to achieve oxidative stress avoidance and synergistic therapy of melanoma using quercetin (Qu)-coated gold nanorod (GNR@PEG).

Low toxicity ginsenoside Rg1-carbon nanodots as a potential therapeutic agent for human non-small cell lung cancer

Here ginsenoside Rg1 was used to synthesise Rg1 carbon nanodots via a one-step hydrothermal method. The surface of the Rg1 carbon nanodots is rich in hydrophilic functional groups with good water solubility and biocompatibility. The Rg1 carbon nanodots exhibited a high inhibitory effect on the proliferation, migration, and proapoptotic ability of non-small cell lung cancer A549 cells. The changes in the levels of ROS, Ca2+, and MMP in A549 cells after the administration of Rg1 carbon nanodots were evaluated and further correlated with relevant proteins in the caspase apoptotic pathway. Proteomic screening revealed that the Rg1 carbon nanodots could regulate A549 cell apoptosis by activating the expression of MAPK pathway-related proteins. In the in vivo experiment, the therapeutic efficacy of the Rg1 carbon nanodots in inhibiting tumour growth was much higher than that of commonly used chemotherapy drugs, with negligible toxicity and side effects. Immunohistochemical staining showed that the expression of caspase- and MAPK pathway-related proteins in mouse tumour tissues was consistent with that at the cellular level. The results suggest that Rg1 carbon nanodots can promote tumour apoptosis and represent a potential therapeutic agent for human non-small-cell lung cancer.

A novel bioassay for thyroid-blocking immunoglobulins.

Thyroid-blocking immunoglobulins (TBI) are present in 10%-15% of patients with autoimmune thyroid disease (AITD). TBI affect thyroid function. The analytical performance of a novel TBI bioassay was evaluated. Sera from AITD patients were tested with a cell-based TBI reporter bioassay (Thyretain®) with the expression of a luciferase transgene as readout and a new "Turbo™" TBI bioassay with a readout based on a cyclic AMP-activated luciferase. All samples were also run on two TSH-R binding immunoassays. A Passing-Bablok regression, a Bland-Altman plot, and user/lot comparisons were performed. In addition, dose-response curves for Turbo and Thyretain were fitted using serial dilutions, and half-maximal and 80% inhibitory concentrations (IC50/IC80) were compared. Of 1,011 unselected AITD patients, 131 patients (212 samples) were TBI positive. Of the 212 samples, 149 (70.3%), 47 (22%), and 16 (7.5%) were hypothyroid, euthyroid, and hyperthyroid, respectively. The three thyrotropin receptor antibody (TSH-R-Ab) assays were negative in 90 controls devoid of autoimmune thyroid disorders. In contrast, the Turbo cyclic adenosine 3',5'-monophosphate (cAMP) TBI, Thyretain TBI, and the binding assays detected TBI in 212 (100%), 168 (79%), and 138/180 (65%) samples, respectively (p< 0.001). Turbo highly correlated with thyroid function (p< 0.001). The percentage inhibition in both Turbo and Thyretain correlated with TSH-R-Ab binding assay positivity (both p< 0.001). The two bioassays correlated (r = 0.8, p< 0.001), and the Bland-Altman plot displayed no significant bias (0.24). Values scatter with slight systemic deviation between TBI mean values of 10%-50% inhibition, with higher Turbo than Thyretain results. Intra-assay validation demonstrated adequate precision with a very low coefficient of variation (average CV 5.4%) and lower CV with samples with a high inhibitory effect (CVAverage= 1.7% for a sample with 95% inhibition Thyretain). CV did not differ between users (p = 0.35) and lots (p = 0.121). The IC50/IC80 values were 1.55 ng/mL/3.48 ng/mL for Turbo and 6.76 ng/mL/18.46 ng/mL for Thyretain, respectively, demonstrating the markedly higher sensitivity of Turbo. The novel, easy-to-perform, rapid, and reliable Turbo TSH-R blocking bioassay detected significantly more TBI than the established immunoassays, emphasizing its higher analytical performance and clinical utility in the management of patients with AITD.

Antiquorum Sensing Effect, Theoretical, and X‐Ray Studies of a Schiff Base Molecule Containing Pyrimidine Nucleus

AbstractCompound 4, a Schiff base‐containing pyrimidine moiety, was synthesized from the reaction of N‐amino pyrimidine derivative with 4‐fluorobenzaldehyde. The molecular and crystallographic structure of 4 was determined by the SC‐XRD method. According to these results, compound 4 crystallized in the triclinic P‐1 space group, and the stability of its crystal structure was ensured through intermolecular C−H⋅⋅⋅π and π⋅⋅⋅π interactions. In addition to the antibacterial effects of the molecule on some Gram‐positive and Gram‐negative bacteria, the inhibition of biofilm formation in P. aeruginosa PAO1 and the production of violacein pigment in Chromobacterium violaceum (C. violaceum) 12472 were studied. The results demonstrated that compound 4 had strong effectiveness in preventing the formation of biofilms produced by PAO1 with an inhibition rate of 69 %. Extensive theoretical calculation studies of molecule have been conducted and the molecular structure of 4 has been optimized in the ground state using density functional theory (DFT). The investigated compound's frontier molecular orbitals, chemical parameters, and molecular electrostatic potential surfaces were examined. Molecular docking studies were performed to explain the binding interaction 4 with the high inhibitory effect against C. violaceum phenylalanine hydroxylase D139A (PDB ID: 4Q3Y), D139E (PDB ID: 4Q3W), D139K (PDB ID: 4Q3Z), and D139N (PDB ID: 4Q3X) mutations.

Impact of Microencapsulation on Ocimum gratissimum L. Essential Oil: Antimicrobial, Antioxidant Activities, and Chemical Composition

Ocimum gratissimum (OG) is a species rich in essential oils (EO), which is known for its antimicrobial and antioxidant properties. This study aimed to encapsulate the essential oil of Ocimum gratissimum (OGE), determine its chemical composition, and evaluate its antioxidant and antimicrobial activities against six pathogenic bacteria, comparing it with the free essential oil (OGF). The EO was extracted by hydrodistillation using a Clevenger-type apparatus, and an oil-in-water emulsion was prepared using a combination of biopolymers: maltodextrin (MA), cashew gum (CG), and inulin (IN). The chemical profile was identified using gas chromatography–mass spectrometry (GC–MS). Antioxidant activity was assessed using the Oxygen Radical Absorbance Capacity with fluorescein (ORAC-FL) method, while the Minimum Inhibitory Concentrations (MIC) and Minimum Bactericidal Concentrations (MBC) were determined by the microdilution method. Microparticles were formed using the spray-drying method, achieving an encapsulation efficiency of 45.2%. The analysis identified eugenol as the main compound both before and after microencapsulation. The OGE microparticles demonstrated high inhibitory and bactericidal effects against S. aureus, S. choleraesuis, and E. coli, with MIC values of 500 µg·mL−1 and MBC values of 1000 µg·mL−1, as well as antioxidant activity of 1914.0 µmol-TE·g−1. Therefore, it can be inferred that the EO of OG maintained its antimicrobial and antioxidant effects even after microencapsulation by spray-drying, making it a promising natural ingredient.

A square planar cobalt(II)-thiosemicarbazone complex. Synthesis, characterization, antiviral and anti-inflammatory potential

Considering the possible antiviral effect of cobalt compounds and known pharmacological potential of thiosemicarbazones, a new combination containing cobalt(II) ions and tetradentate thiosemicarbazone was synthesized and structurally analyzed. In the complex structure (Co1), the cobalt ion is in 2+ oxidation state and is coordinated with ONNO donor set on the thiosemicarbazone backbone. The complex molecule crystallizes in the space group P21/m and the environment of the cobalt center tends to square planar geometry. The inhibitory performance of SARS-CoV-2 and the anti-inflammatory impact of the complex molecule were investigated. It was found that Co1 has high inhibitory effects on the SARS-CoV-2 virus's 3CL main protease enzyme, ACE2:SARS-CoV2 Spike RBD interaction, and IL8. Also, it showed significant anti-inflammatory effects on the release of IL6, IL8, IL10, and TGFβ1 cytokines and wound healing during in vitro TNF-α-induced inflammation. Experimental evidence demonstrates that Co1 diminishes both IL8 gene expression and protein levels. According to in silico and experimental results, it has a drug potential. Assessing the in vivo impacts of Co1 might contribute to understanding its potential as an antiviral and anti-inflammatory agent.

One-step hydrothermal synthesis of F,N,S-doped photoluminescent carbon dots with yellowish-orange emission for sensitive Cu2+ ion detection: Environmental and biomedical applications

Herein, fluorine-, nitrogen-, and sulfur-doped carbon dots (FNS-CDs) were prepared via a one-step hydrothermal synthesis using flufenamic acid and thiourea as precursors, which showed yellowish-orange fluorescence both in aqueous solution and in the solid state. The as-prepared FNS-CDs were monodisperse and had an average diameter of 4 nm, good water solubility, a fluorescence quantum yield of 18.63 %, and excellent pH and ionic strength stability. The optimal excitation/emission wavelengths of the FNS-CDs were 406/570 nm, with an excitation-dependent wavelength range of 365–435 nm. The surface states, morphologies, and elemental compositions of the FNS-CDs were characterized using FTIR, XRD, TEM, and XPS. In addition, the FNS-CDs without any further modification exhibited high selectivity and sensitivity as nanosensors for Cu2+ over other metal ions. The PL quenching phenomenon can be used to detect Cu2+ ions within a linear range of 1–25 μM with a detection limit of 83.10 nM and an association constant of 1.29 × 104 M−1. The PL of the FNS-CDs was significantly quenched by Cu2+ ions through static quenching and was restored upon the subsequent addition of EDTA. The practical application was demonstrated through the detection of Cu2+ ions in real water samples, yielding recovery rates ranging from 97.8 % to 103.9 % with an RSD below 2.5 %. The FNS-CDs/Cu2+ complex exhibits potent antibacterial activity against S. aureus (85.27 %±2.1 %) and E. coli (91.31 %±1.6 %), whereas the FNS-CDs/Cu2+ has a higher inhibitory effect on the growth of E. coli. Furthermore, the FNS-CDs (100 μg/mL) were used for cell imaging, showing low toxicity to HCT-116 cells exhibited yellowish-orange fluorescence under a confocal microscope.

Silver secnidazole nano-hybrid emulsion-based probiotics as a novel antifungal formula against multidrug-resistant vaginal pathogens.

This study presents a novel approach to manage vaginal infections due to Candidiasis, utilizing a novel silver secnidazole nano-hybrid emulsion (Ag-Secn-NHE)-based probiotics and free Ag-Secn-NHE. Ag-Secn-NHE was prepared by simple homogenization‒ultrasonication technique and validated by using a ultraviolet‒visible scan, dynamic light scattering, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, and zeta potential. Saccharomyces cerevisiae (RCMB 002Y001) is the most effective probiotic-producing organism that demonstrates significant effects when combined with Ag-Secn-NHE. Ag-Secn-NHE-based probiotics showed significant antifungal effect compared to free Ag-Secn-NHE, silver nitrate, silver nanoparticles, secnidazole, secnidazole nanoemulsion, and commercial vaginal wash against multidrug-resistant vaginal pathogens. The highest inhibitory effect was achieved with Ag-Secn-NHE-based probiotic against Candida auris, Candida albicans, and Cryptococcus neoformans with minimal inhibitory concentration (MIC) 0.625±0.002, 0.00625:1.25±0.012 and 0.00625:1.25±0.032mg/mL, respectively, in comparison with Ag-Secn-NHE that show MIC at 0.00625:1.25±0.612, 0.0125:2.5±0.812, and 0.0125:2.5±0.112mg/mL (Ag:Secn). Ag-Secn-NHE-based- probiotic show minimum fungicidal concentration (MFC) at range from 2.5 to 20mg/mL, wherever free Ag-Secn-NHE show MFC range from 5 to >20mg/mL. Additionally, Ag-Secn-NHE-based probiotics have 75% inhibition of biofilm formation against C. auris and 60% inhibition of biofilm formation against both Cryptococcus neoformans and C. albicans in comparison with free Ag-Secn-NHE. Time-kill curves showed that the antifungal effect of Ag-Secn-NHE-based probiotics was fungistatic at 2MIC value after 4h and after 16h for Ag-Secn-NHE. TEM photographs showed that C. auris cells treated with Ag-Secn-NHE-based probiotic formula revealed severe deformations and distored ultrastructural changes. furthermore, results indicated that the Gamma radiation up to 15kGy increases production of Ag-Secn-NHE in comparison with non-irradiated one.

Investigation of the Synergistic Effect of Rosehip Vinegar and Propolis Extract on Antibacterial and Antibiofilm Efficacy Against Foodborne Pathogens and Their Protective Effect on Sardine (Sardina pilchardus)

ABSTRACT The antibacterial and antibiofilm effects of rosehip vinegar and propolis extract, separately and as a mixture, were investigated on Staphylococcus aureus and Escherichia coli O157:H7. The organoleptic properties and tissue integrity of sardine fish treated with this mixture were evaluated. The propolis extract was found to have a higher inhibitory effect (>80%) on S. aureus (up to the 5th dilution) than on E. coli O157:H7 (only at the first dilution). A potential synergistic antibacterial and antibiofilm effect of the mixture was observed with an inhibition ratio of ≥50%. This mixture may extend the shelf life of sardines as a natural antibacterial/antibiofilm preservative.

Phytochemical profiles, bioactivities, and molecular docking and molecular dynamics approaches of endemic Campanula baskilensis Behçet (campanulaceae)

Campanula species have phenolic derivatives with a broad biological potential. This study aimed to investigate the chemical contents, bioactivities, and prediction of the biological effect mechanism using the molecular docking study for C. baskilensis (CB) leaf (L), root (R), and stem (S) extracts.CBL gave the highest phenolic contents as hesperidin at 7.56 mg/g extract. Total phenolic and flavonoid contents of CBS were determined as 3.12 ± 0.05 mg GAE/g and 1.11 ± 0.11 mg QE/g, respectively. CBS and CBL exhibited high DPPH• scavenging, H2O2 scavenging, AChE, BChE, carbonic anhydrase, lipase, and tyrosinase inhibition effects and demonstrated potent antimicrobial activity. The strong phenolic components of CBS and CBL extracts contributed to their biological activities. According to the molecular docking results, a high inhibition effect was observed on the inhibition activities due to the presence of hesperidin, which is the highest main component of the extracts. Additionally, docking studies were performed on hesperidin for the first time. Dynamics study showed that the interaction between the hesperidin and BChE increased stability, producing a stable complex form within 100 ns. In conclusion, C. baskilensis extracts, especially hesperidin, may be promising potential sources for neurological diseases and complementary medicine.

Discovering Novel Bioherbicides: The Impact of Hemp-derived Phytocannabinoid Applications on Zea mays L. and Relevant Weeds

In addition to competition, phytotoxic plant metabolites contribute to the weed-suppressing properties of cover crops, which could be the basis for the development of novel bioherbicides. We investigated the impact of five Cannabis sativa L. -derived neutral phytocannabinoids and an aqueous C. sativa tissue extract (HE) at six concentrations on the germination rate (GR) and seedling root length (RL) of Zea mays L., two monocotyledonous and two dicotyledonous weed species in laboratory Petri dish bioassays. Additionally, the effect of pre-emergence applications of HE, cannabidiol (CBD), and cannabidivarin (CBDV) formulations on GR and shoot dry matter (SDM) were examined in greenhouse pot studies. The effects of phytocannabinoids and HE were analyzed in dose-response curves. For the highest rates, the effects on GR, RL and SDM were calculated by ANOVA and HSD test (p < 0.05). HE exhibited the greatest suppression on GR and RL for all plant species in the Petri dish bioassay, with RGR, RL exceeding −90%. Phytocannabinoids reduced mainly RL of all plants and decreased the GR of most weed species. Effects varied among plants and phytocannabinoids, with CBDV and CBD showing similar high inhibitory effects on RL as HE in the Petri dish bioassay. All pre-emergence applications resulted in a positive RGR across all studied plants and in a positive RSDM in Z. mays and Echinochloa crus-galli (L.) P. Beauv, whereas in the other weed species the RSDM was negative. In conclusion, phytocannabinoids play a major role in weed suppression of HEs. CBDV and CBD are the most promising candidates for bioherbicide development especially against annual dicotyledonous weed species.

Green Biosynthesis and Biological Properties of Copper Oxide Nanoparticles Using Paulownia Tomentosa Plant Extracts

AbstractCopper oxide nanoparticles have attracted a great deal of attention in many fields due to their attractive physico‐chemical properties. In particular, their synthesis using an environmentally friendly method offers advantages in many applications. In the present report, copper oxide nanoparticles are produced from extracts of the plant Paulownia tomentosa by a method of biosynthesis. The synthesized CuO NPs have been characterized morphologically and structurally by fourier transform infrared spectroscopy, scanning electron microscopy, energy‐dispersive X‐ray analysis, and X‐ray diffraction. Furthermore, the antimicrobial, antibiofilm and anticancer activities of the synthesized CuO NPs were evaluated. The CuO NPs were spherical and the particle size was 12.5 nm. For the tested microorganisms, CuO NPs showed a high inhibitory effect in terms of antimicrobial and antibiofilm activity. The cytotoxicity of the synthesized CuO NPs against HT‐22 and MCF‐7 showed a dose‐response activity. 50 % inhibitory concentration values were found to be 18.34 and 14.32 μg/mL of CuO NPs against the HT‐22 and MCF‐7 cancer cells, respectively. The results suggest that these nanoparticles can be used as effective antibacterial, antibiofilm and anticancer agents in the biomedical fields.

Development of fucoidan/polyethyleneimine based sorafenib-loaded self-assembled nanoparticles with machine learning and DoE-ANN implementation: Optimization, characterization, and in-vitro assessment for the anticancer drug delivery

This study aims to develop sorafenib-loaded self-assembled nanoparticles (SFB-SANPs) using the combined approach of artificial neural network and design of experiments (ANN-DoE) and to compare it with other machine learning (ML) models. The central composite design (CCD) and ML algorithms were used to screen the effects of concentrations of both the polymers (polyethyleneimine and fucoidan) on the outcome responses, i.e., particle size and entrapment efficiency with defined constraints. The prediction from different ML models (bootstrap forest, K-nearest neighbors, artificial neural network, generalized regression-lasso and support vector machines) were compared with ANN-DoE model. The ANN-DoE model showed better accuracy and predictability and outperformed all the other models. This depicted that the concept of using ANN and DoE combination approach provided the best, uncomplicated and cost-effective way to optimized the nanoformulations. The optimized formulation generated from the ANN-DoE combined model was further evaluated for characterization and anticancer activity. The optimized SFB-SANPs were prepared using the polyelectrolyte complexation method with Polyethyleneimine (PEI) as a cationic polymer and fucoidan (FCD) as an anionic. The SFB-SANPs were nanometric in size (280.4 ± 0.089 nm) and slightly anionic in nature (zeta potential = −6.03 ± 0.92 mV) with an encapsulation efficiency of 95.56 ± 0.30 %. The drug release from SFB-SANPs was controlled and sustained in the cancer microenvironment (pH 5.0). The SFB-SANPs were compatible with red blood cells (RBCs), and the % hemolysis was found to be <5.0 %. The anticancer activity of the SFB-SANPs exhibited an IC50 at 2.017 ± 0.516 μM against MDMB-231 cells, showing a significantly high inhibitory effect on breast cancer cell lines. Therefore, the nanocarriers developed using various ML tools inherit a huge promise in anticancer drug delivery.

In-vitro Antimicrobial Activity of Mtad, Photoactivated Disinfection Along with Chlorohexidine on Enterococcus faecalis, Staphylococcus aureus and Candida albicans

This study evaluated the antimicrobial activity of five root canal irrigants against MTCC of Enterococcus faecalis, Staphylococcus aureus, Candida albicans, in-vitro study of the inhibitory activity of PAD in conventional Endodontic Treatment (CET) and also combination of CET with PAD (CHX+PAD). All of these microorganisms were incubated in the presence of an Endodontic irrigant. Agar diffusion tests were performed and colony counts were tested using paper point to evaluate the inhibitory effect of the irrigants. The mean diameters of the inhibition zones for C. albican were 21mm 3% Naocl, 19mm CHX, 0.7PAD, 22mm CHX+PAD, 20mm Fluconazole, 18mm Doxycycline. The zone diameters of the inhibition zones of Enterococcus faecalis were 17mm 0.5% Naocl, 18mm CHX, 12mmPAD, 35mm MTAD, and 19mm PAD+CHX. The Zone Diameter of the inhibition zones of Staphylococcus aureus were 18mmCHX, 12mm PAD, 19mm PAD+CHX, 25mm MTAD, and 19mm 3% NaoCl. Together High inhibitory effect was detected for PAD+CHX and MTAD on all three pathogens. Candida showed more inhibition to all irrigants followed by Staphylococcus aureus and Enterococcus faecalis.

Design of new α-glucosidase inhibitors based on the bis-4-hydroxycoumarin skeleton: Synthesis, evaluation, and in silico studies

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose.

Inhibitory Effects, Fluorescence Studies, and Molecular Docking Analysis of Some Novel Pyridine-Based Compounds on Mushroom Tyrosinase.

Melanin biosynthesis in different organisms is performed by a tyrosinase action. Excessive enzyme activity and pigment accumulation result in different diseases and disorders including skin cancers, blemishes, and darkening. In fruits and vegetables, it causes unwanted browning of these products and reduces their appearance quality and economic value. Inhibiting enzyme activity and finding novel powerful and safe inhibitors are highly important in agriculture, food, medical, and pharmaceutical industries. In this regard, in the present study, some novel synthetic pyridine-based compounds including 2,6-bis (tosyloxymethyl) pyridine (compound 3), 2,6-bis (butylthiomethyl) pyridine (compound 4), and 2,6-bis (phenylthiomethyl) pyridine (compound 5) were synthesized for the first time, and their inhibitory potencies were assessed on mushroom tyrosinase diphenolase activity. The results showed that while all tested compounds significantly decreased the enzyme activity, compounds 4 and 5 had the highest inhibitory effects (respectively, 80 and 89% inhibition with the IC50 values of 17.0 and 9.0 μmol L-1), and the inhibition mechanism was mixed-type for both compounds. Ligand-binding studies were carried out by fluorescence quenching and molecular docking methods to investigate the enzyme-compound interactions. Fluorescence quenching results revealed that the compounds can form nonfluorescent complexes with the enzyme and result in quenching of its intrinsic emission by the static process. Molecular docking analyses predicted the binding positions and the amino acid residues involved in the interactions. These compounds appear to be suitable candidates for more studies on tyrosinase inhibition.