Inhibition of protein misfolding and aggregation by steroidal quinoxalin-2(1H)-one and their molecular docking studies.

A series of D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one attached to an electron-releasing (ER) or electron-withdrawing (EW) groups via steroidal oxoacetate intermediate were synthesized to investigate their protein aggregation inhibition potential using human lysozyme (HLZ). The influence of the type of substituent at the C-6 positions of the quinoxalin-2(1H)-one ring on the protein aggregation inhibition potential was observed, showing that the EW moiety improved the protein aggregation inhibition potency. Of all the evaluated compounds, NO2-substituted quinoxalin-2(1H)-one derivative 13 was the most active compound and had a maximum protein aggregation inhibition effect. Significant stabilization effects strongly support the binding of the most biologically active steroidal quinoxalin-2(1H)-one with docking studies. The predicted physicochemical and ADME properties lie within a drug-like space which shows no violation of Lipinski's rule of five except compounds 12 and 13. Combined, our results suggest that D-ring fused 16-substituted steroidal quinoxalin-2(1H)-one has the potential to modulate the protein aggregation inhibition effect.

Energy storage and water splitting applications of self-grown Na2O-NiCl2 upright standing nanoplates: a process of 3D nickel surface modification using seawater.

The recent trend in research fosters the use of abundant seawater for modifying metal surfaces as electrode materials for energy generation, storage, transport, and water-splitting technologies. Economic and ecofriendly seawater is used as a solvent for modifying the surface of 3D nickel-foam (NiF) to Na2O-NiCl2@NiF as an electrode material in electrochemical supercapacitors and water-splitting electrocatalysis applications. The phase of the as-obtained Na2O-NiCl2 is confirmed from the proposed reaction mechanism, followed various physical measurement tests such as X-ray photoelectron spectroscopy and Fourier transform infrared analysis. The formation of Na2O-NiCl2 is caused by a high operation temperature and pressure of seawater solvent, the presence of lone pair electrons on oxygen, and more reactivity of Na for combining with dissolved oxygen than the lone-pair free Cl (towards Ni). In addition to exceptional HER and OER electrocatalytic activities, i.e., 146.3 mV cm-2 and 217 mV cm-2 at a scan rate of 5 mV s-1 to attain the 10 mA cm-2 current density, the Na2O-NiCl2 has demonstrated moderate energy storage ability with considerable durability, i.e., 2533 F g-1 specific capacitance at 3 A g-1 current density even after 2000 redox cycles. The as-assembled Na2O-NiCl2//Na2O-NiCl2 symmetric electrochemical supercapacitor device has ignited a "CNED" panel consisting of nearly forty LEDs with full brightness, offering applied importance in home appliances. In nutshell, seawater-modified metal surfaces can be used for energy storage and water-splitting applications.

Toxicological assessment of Phormidium sp. derived copper oxide nanoparticles for its biomedical and environmental applications.

Driven by the need to biosynthesized alternate biomedical agents to prevent and treat infection, copper oxide nanoparticles (CuONPs) have surfaced as a promising avenue. Cyanobacteria-derived synthesis of CuONPs is of substantive interest as it offers an eco-friendly, cost-effective, and biocompatible route. In the present study biosynthesized CuONPs were characterized and investigated regarding their toxicity. Morphological analysis using TEM, SEM and AFM showed the spherical particle size of 20.7 nm with 96% copper that confirmed the purity of CuONPs. Biogenic CuONPs with IC50 value of 64.6 µg ml-1 showed 90% scavenging of free radicals in superoxide radical scavenging assay. CuONPs showed enhanced anti-inflammatory activity by 86% of protein denaturation with IC50 value of 89.9 µg ml-1. Biogenic CuONPs exhibited significant toxicity against bacterial strains with lowest MIC value of 62.5 µg ml-1 for B. cereus and fungal strain with a MIC value of 125 µg ml-1 for C. albicans. In addition CuONPs demonstrated a high degree of synergistic interaction when combined with standard drugs. CuONPs exhibited significant cytotoxicity against non-small cell lung cancer with an IC50 value of 100.8 µg ml-1 for A549 and 88.3 µg ml-1 for the H1299 cell line with apoptotic activities. Furthermore, biogenic CuONPs was evaluated for their photocatalytic degradation potential against methylene blue dye and were able to removed 94% dye in 90 min. Free radical scavenging analysis suggested that CuONPs assisted dye degradation was mainly induced by hydroxide radicals. Biogenic CuONPs appears as an eco-friendly and cost effective photocatalyst for the treatment of wastewater contaminated with synthetic dyes that poses threat to aquatic biota and human health. The present study highlighted the blend of biomedical and photocatalytic potential of Phormidium derived CuONPs as an attractive approach for future applications in nanomedicine and bioremediation.

Synthesis, Anti-Fungal Potency and In silico Studies of Novel Steroidal 1,4-Dihydropyridines.

Working principle of azoles as antifungals is the inhibition of fungal CYP51/lanosterol-14α-demethylase via selective coordination with heme iron. This interaction can also cause side effects by binding to host lanosterol-14α-demethylase. Hence, it is necessary to design, synthesize and test new antifungal agents that have different structures than those of azoles and other antifungal drugs of choice in clinical practice. Consequently, a series of steroidal 1,4-dihydropyridine analogs 16-21 were synthesized and screened for their in vitro anti-fungal activity against three Candida species as steroids-based medications have low toxicity, less vulnerability to multi-drug resistance, and high bioavailability by being capable of penetrating the cell wall and binding to specific receptors. Initially, Claisen-Schmidt condensation takes place between steroidal ketone (dehydroepiandrosterone) and an aromatic aldehyde forming steroidal benzylidene 8-13 followed by Hantzsch 1,4-dihydropyridine synthesis resulting in steroidal 1,4-dihydropyridine derivatives 16-21. The results exhibited that compound 17 has significant anti-fungal potential with an MIC value of 750 µg/ml for C. albicans and C. glabrata and 800 µg/ml for C. tropicalis. In silico molecular docking and ADMET studies were also performed for compounds 16-21.

Synthesis, antifungal evaluation, and molecular docking studies of steroidal thiazolopyrimidines.

A series of steroidal thiazolopyrimidine derivatives were developed and evaluated for their antifungal properties against Candida species using steroid as the basic skeletonand a thiazolopyrimidine heterocycle as a pharmacophore in the D-ring. Dehydroepiandrosterone, aromatic aldehydes, and 2-aminothiazole were used in a one-pot multicomponent reaction with silica sulphuric acid to generate the target molecules. Additionally, molecular docking studies were conducted to determine how synthesized steroidal derivatives interacted with the amino acid residues of CYP51 ofCandida albicans.

Microwave-assisted one-pot multicomponent synthesis of steroidal pyrido[2,3-d]pyrimidines and their possible implications in drug development.

Protein misfolding can lead to fibrillar and non-fibrillar deposits which are the signs of countless human diseases. A promising strategy for the prevention of such diseases is the inhibition of protein aggregation, and the most crucial step toward effective prevention is the development of small molecules having the potential for protein-aggregation inhibition. In this search, a series of novel steroidal pyrido[2,3-d]pyrimidines have been synthesized employing steroidal ketone, substituted aldehydes, and 2,6-diaminopyrimidin-4(3H)-one through the microwave-assisted one-pot multicomponent methodology. The aggregation inhibition potential of newly synthesized compounds was evaluated on human lysozyme (HLZ). All the synthesized compounds were found to be efficient in the inhibition of protein aggregation in carefully designed in vitro experiments. Moreover, molecular docking studies also determine the binding interactions between all the synthesized compounds and native HLZ through hydrogen bonding. The structures of synthesized compounds were also elucidated using various spectroscopic techniques.

Investigation of morphological and biochemical changes of zinc oxide nanoparticles induced toxicity against multi drug resistance bacteria.

BACKGROUND: Biofilms are microbial colonies that remain enclosed in an organic polymeric matrix substance on biotic and abiotic surfaces, allowing them to colonize medical equipments and involved in most device associated life intimidating infections. Due to their antimicrobial resistance there is an urgent need to discover novel biofilm preventive and therapeutic agents. METHODS: ZnO NPs were synthesized using cyanobacteria Gleocapsa gelatinosa cell extract through green and cost-effective approach. Physiochemical characterization was done to determine their morphologies and size distribution. Antibiofilm and eradication activity of ZnO NPs was determined. Cell viability and internalization ability of ZnO NPs into biofilm was analyzed by flow cytometry. Confocal microscopy was done to visualize the disrupted biofilm morphology treated with ZnO NPs. RESULTS: It was observed that ZnONPs were spherical in shape with 31-35 nm size and were moderately dispersed. ZnO NPs exhibited high antibiofilm activity against B. cereus and E. coli with minimum biofilm inhibitory concentration (MBIC) of ZnO NPs at 46.8 µg ml-1 and 93.7 µg ml-1. Flow cytometry analysis confirmed the reduced bacterial cell viability due to increased permeability, altered bacterial growth and enhanced production of intracellular ROS. Disruption of membrane integrity exhibited with reduced exopolysaccharides secretion and leakage of nucleic acids through UV-Vis spectroscopy. Results of confocal microscopy highlighted strong interaction of ZnO NPs with intracellular components leading to biofim destruction. CONCLUSIONS: This study emphasizes the potential mechanisms underlying the selective bactericidal properties of ZnO NPs and highlighted the strong interaction of ZnO NPs with intracellular components leading to biofim destruction. Therefore, ZnO NPs could be considered as a promising antibiofilm agent and thus could expand the possibility to use as therapeutic agent.

Screening, characterisation and bioactivities of green fabricated TiO2 NP via cyanobacterial extract.

The present study was aimed at exploring 37 strains of cyanobacteria for the biofabrication of TiO2 NP and evaluation of their antioxidant, antifungal, antibacterial and hemolytic activity. Screening of cyanobacterial strains was done via SEM, followed by optimisation and characterisation of the best strain. Synechocystis NCCU-370 appeared as the best strain for the synthesis of TiO2 NP in terms of size (73.39 nm) and time (24 h) after screening. Following optimisation, nanoparticles were synthesised in 12 h having an average grain size of 16 nm. The aqueous extract preparation required heating of 5 mg/ml of powdered biomass to 60 °C for 10 min. Optimum conditions for the synthesis of TiO2 NP were found to be pH 7, 30 °C and 12-h cell extract exposure to 0.1 mM of salt. Antioxidant activity was evaluated via DPPH, ABTS and FRAP assay. Antifungal potential was explored against Candida albicans (MIC = 125 µg/ml), Candida glabrata (MIC = 500 µg/ml) and Candida tropicalis (MIC = 250 µg/ml), whereas antibacterial potential was gauged for Bacillus cereus (MIC = 31.25 µg/ml), Escherichia coli (MIC = 31.25 µg/ml) and Klebsiella pneumoniae (MIC = 500 µg/ml) strains. Biogenic TiO2 NP demonstrated partial synergistic effect and excellent biocompatibility.

A review on synthesis and biological activities of D-ring modified pregnenolone.

Steroids are polycyclic compounds and are broadly exist in the natural world and display various biological activities. Many steroidal compounds have been used as traditional medicines, for example, antibacterial and few as hormone like medication. The introduction of heterocycle or heteroatom in the steroidal moiety has a significant biological impact. These derivatives have widespread biological activities such as anticancer, anti-inflammatory, anti-ulcer and antimicrobial. The present article is a brief review of the recent development of synthesis and biological activities of pregnenolone derivatives.

Effects of dietary protein levels on growth, feed utilization, protein retention efficiency and body composition of young Heteropneustes fossilis (Bloch).

An 8-week growth trial was conducted to assess the effect of dietary protein on growth, feed utilization, protein retention efficiency, and body composition of young Heteropneustes fossilis (10.02 +/- 0.09 g; 9.93 +/- 0.07 cm). Isocaloric (4.15 kcal g(-1), GE) diets with varying levels of protein (25, 30, 35, 40, 45, and 50% of the diet) were fed near to satiation to triplicate groups of fish. Optimum dietary protein was determined by analyzing live weight gain (LWG%), feed conversion ratio (FCR), protein efficiency ratio (PER), specific growth rate (SGR%), and protein retention efficiency (PRE%) data. Maximum LWG% (167), best FCR (1.42), PER (1.75), SGR (1.76), and PRE (31.7%) were evident in fish fed 40% protein diet (Diet 4). Body protein data also supported the above level. However, second-degree polynomial regression analysis of the above data indicated that inclusion of dietary protein in the range of 40-43% is optimum for the growth of young H. fossilis.