Virtual Screening for Potential Phytobioactives as Therapeutic Leads to Inhibit NQO1 for Selective Anticancer Therapy

NAD(P)H:quinone acceptor oxidoreductase-1 (NQO1) is a ubiquitous flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory two-electron reductions of quinones, quinonimines, nitroaromatics, and azo dyes. NQO1 is a multifunctional antioxidant enzyme whose expression and deletion are linked to reduced and increased oxidative stress susceptibilities. NQO1 acts as both a tumor suppressor and tumor promoter; thus, the inhibition of NQO1 results in less tumor burden. In addition, the high expression of NQO1 is associated with a shorter survival time of cancer patients. Inhibiting NQO1 also enables certain anticancer agents to evade the detoxification process. In this study, a series of phytobioactives were screened based on their chemical classes such as coumarins, flavonoids, and triterpenoids for their action on NQO1. The in silico evaluations were conducted using PyRx virtual screening tools, where the flavone compound, Orientin showed a better binding affinity score of −8.18 when compared with standard inhibitor Dicumarol with favorable ADME properties. An MD simulation study found that the Orientin binding to NQO1 away from the substrate-binding site induces a potential conformational change in the substrate-binding site, thereby inhibiting substrate accessibility towards the FAD-binding domain. Furthermore, with this computational approach we are offering a scope for validation of the new therapeutic components for their in vitro and in vivo efficacy against NQO1.     

Redox‐Active Peptide‐Functionalized Quinquethiophene‐Based Electrochromic π‐Gel

An electrochromic system based on a self‐assembled dipeptide‐appended redox‐active quinquethiophene π‐gel is reported. The designed peptide‐quinquethiophene consists of a symmetric bolaamphiphile that has two segments: a redox‐active π‐conjugated quinquethiophene core for electrochromism, and peptide motif for the involvement of molecular self‐assembly. Investigations reveal that self‐assembly and electrochromic properties of the π‐gel are strongly dependent on the relative orientation of peptidic and quinquethiophene scaffolds in the self‐assembly system. The colors of the π‐gel film are very stable with fast and controlled switching speed at room temperature.     

Magnetic molecularly imprinted polymer nanoparticles for dispersive micro solid-phase extraction and determination of buprenorphine in human urine samples by HPLC-FL

A simple, sensitive and accessible while reliable method was developed and validated for quantitation of buprenorphine (Bup) as a highly lipophilic drug in human urine samples. The proposed method is based on a rapid and easy dispersive micro solid-phase extraction procedure using magnetic molecularly imprinted polymer nanoparticles (MMIPNPs), magnetite (Fe₃O₄) cores surrounded by polyamidoamine and Bup as template, followed by high-performance liquid chromatographic analysis with fluorescence detector (HPLC-FL). The prepared MMIPNP adsorbent was characterized by different techniques. Transmission electron microscopy images show that the Fe₃O₄ core nanoparticles are well enwrapped by MIP layers. In determination process, Bup could be quantitatively extracted using MMIPNPs and then can be easily desorbed by mixture of sodium hydroxide (0.1 mol/L) and methanol (1:9, v/v) solution before injection to HPLC. The relative recoveries of Bup were found to be 97.4–100.3%, and the linear dynamic range was within the ranges of 1–1000 ng/mL with R² of 0.9998. Remarkably high quality of 0.21 and 0.71 ng/mL was obtained as the limit of detection and limit of quantification, respectively. The developed method was successfully applied for determination of Bup in infected human urine samples.     

Cold atmospheric plasma modification of curcumin loaded in tri‐phosphate chitosan nanoparticles enhanced breast cancer cells apoptosis

The anti‐cancer mechanisms of curcumin have been reported to include suppressions of angiogenesis and tumor proliferation. The main goal of this research is to increase the solubility of curcumin by cold atmospheric plasma (CAP) and assess the effects of modified curcumin by charging with tri‐polyphosphate chitosan nanoparticles for MCF‐7, MDA‐MB‐231 breast cancer cells, and human fibroblast cells. Curcumin modification was done by CAP and its solubility was evaluated by spectrophotometry. After loading modified curcumin into nano‐chitosan‐TPP, nanocurcumin was characterized by scanning electron microscopy. Cellular viability and apoptosis of treated cells were assessed by MTT and Annexin V. The changes of messenger RNA expression of TP5353 and VEGF genes were analyzed by real‐time PCR. CAP was able to transform the curcumin to possess hydrophilic characteristics after 90 seconds. The mean diameter of Curcumin loaded chitosannanoparticles (NPs) were determined as 48 nm. MTT results showed that the IC₅₀ of nano Cur‐chitosan‐TPP was effectively decreased compared to free curcumin in MCF‐7 (15 μg/mL at 72 hours vs 20 μg/mL at 48 hours). Additionally, nano Cur‐chitosan‐TPP had no significant effect on normal cells (Human dermal fibroblas: HDF), whereas it also decreased the viability of triple negative breast cancer cell line (MDA‐MB‐231). Real‐time PCR results showed that expression level of TP53 gene was upregulated (P = .000), whereas VEGF gene downregulated (P = .000) in treated MCF‐7 cells. Curcumin loaded chitosan nanoparticles have led to an induction of apoptosis (79.93%) and cell cycle arrest (at S and G2M). Modified‐curcumin‐tri‐polyphosphate chitosan nanoparticles using CAP can be considered as a proper candidate for breast cancer treatment.     

Electrochemical preparation of orthophenylenediamine on different cathodes in sulfuric acid

The electrochemical reduction of nitro group of orthonitroaniline (ONA) is carried out on Pb, Cu, and Sn electrodes. The effect of current density, temperature, and acid concentration on product yield is studied. The polarization curve for ONA in acidic condition is recorded. Under preparative electrolysis, ONA gives a mixture of hydroxylamine and phenylenediamine, the proportion of phenylenediamine increasing with the electrolysis time. The product formation is confirmed by thin-layer chromatography, melting-point test, UV-visible, IR, and NMR methods. The operating conditions are optimized for a good yield of orthophenylenediamine. The catalytic activity of different metals for the reduction of nitro group is discussed. The percent yield of orthophenylenediamine is found to be high on the lead electrode. Published in Russian in Elektrokhimiya, 2007, Vol. 43, No. 2, pp. 215–221. The text was submitted by the authors in English.     

Diastereodivergent Catalysis Using Modularly Designed Organocatalysts: Synthesis of both cis‐ and trans‐Fused Pyrano[2,3‐b]pyrans

Both enantiomers of cis‐ and trans‐fused 3,4,4a,8a‐tetrahydro‐2H,5H‐pyrano[2,3‐b]pyran‐7‐carboxylates have been obtained in high diastereoselectivities and enantioselectivities from the same starting materials using a tandem inverse‐electron‐demand hetero‐Diels–Alder/oxa‐Michael reaction catalyzed by modularly designed organocatalysts (MDOs). Diastereodivergence was achieved in these reactions through the direct control of the stereochemistry of the bridgehead atoms of the fused ring using new MDOs self‐assembled from both enantiomers of proline and cinchona alkaloid thiourea derivatives.     

Film formation from monodisperse acrylic lattices 2. Influence of drying temperature on the film formation process

The influence of drying temperature on the properties of latex films was investigated by gravimetry, turbidimetry (i.e., analysis of transmission spectra and interference), atomic force microscopy and measurement of water vapor permeability. Several pitfalls in the determination of water content of dried films that absorb water after being submerged in it have been proposed, such as fading boundaries, remaining water after drying and change of particle sizes. At moderately higher temperatures film formation is improved. This improvement follows from the formation of smoother film surfaces (AFM), lower water vapor permeabilities and smaller values for delta lambda(min). On the other hand, defects as cracks and channels also are created, especially at high temperatures. It appears, however, that these channels do not run from the one surface of a film to the other.     

Effect of fuel content on formation of zinc aluminate nano and micro-particles synthesised by high rate sol–gel autoignition of glycine-nitrates

The autoignition technique using glycine as fuel and related nitrate salts as an oxidiser is able to produce zinc aluminate spinel. The precursors were synthesised with lean and rich fuel at pH of 7.0 and the materials so obtained were calcined at various temperatures ranging from 600–1200°C. The autoignition process of precursors was studied by the simultaneous thermo-gravimetric and differential thermal analyses to determine the ignition mechanism. The calcined powders were characterised by X-ray diffraction, Brunauer–Emmett–Teller technique and transmission electron microscopy. The product contains nano-sized particles with an average size of approximately 20 nm. The XRD patterns showed the formation of ZnO in the powder obtained by the fuel-rich precursor and calcined at 600 C which disappears at 800 C due to solid-state reaction and proper crystallisation after heat treatment. The results presented here can be useful in manufacturing nano and micro-sized ZnAl₂O₄ on an industrial scale using the combustion technique.