Improving the selective naked-eye detection of COVID-19 mediated by simultaneously using three different target oligonucleotides coated on plasmonic AuNPs/hexagonal Ag@AuNPs.

The localized surface plasmon resonance (LSPR) phenomenon provides a versatile property in biosensor technology. This uncommon feature was utilized to produce a homogeneous optical biosensor to detect COVID-19 by the naked-eye readout. In this work, we synthesized two types of plasmonic nanoparticles: (i) AuNPs and (ii) hexagonal core-shell nanoparticles-Au shell on AgNPs (Au@AgNPs). We report herein the development of two colorimetric biosensors employing the efficient targeting and the binding ability for three regions of the COVID-19 genome, that is, S-gene, N-gene and E-gene, at the same time. Two AuNPs and Ag@AuNPs individually coated with three different targets oligonucleotide sequence (TOs) (AuNPs-TOs-mix and Ag@AuNPs-TOs-mix) for simultaneous detection of S-gene, N-gene and E-gene of the COVID-19 virus, using the LSPR and naked-eye methods in the laboratory and biological samples. The target COVID-19 genome RNA detected using the AuNPs-TOs-mix and Ag@AuNPs-TOs-mix can achieve the same sensitivity. The detection ranges by the AuNPs-TOs-mix and Ag@AuNPs-TOs-mix are both sufficiently improved in equal amounts in comparison to any of the AuNPs-TOs and Ag@AuNPs-TOs. The sensitivity of the current COVID-19 biosensors were 94% and 96% based on the number of positive samples detected for AuNPs-TOs-mix and Ag@AuNPs-TOs-mix, respectively. Moreover, all the real-time PCR confirmed negative samples obtained the same results by the biosensor; accordingly, the specificity of this approach got to 100%. The current study reports a selective, reliable, reproducible and visual 'naked-eye' detection of COVID-19, devoid of the requirement of any sophisticated instrumental techniques.Communicated by Ramaswamy H. Sarma.

Synthesis, anticancer activity, and ß-lactoglobulin binding interactions of multitargeted kinase inhibitor sorafenib tosylate (SORt) using spectroscopic and molecular modelling approaches.

Sorafenib tosylate (SORt) is an oral multikinase inhibitor used for treatment of advanced renal cell, liver, and thyroid cancers. In this study, this drug was synthesized and its antiproliferative activities against HCT116 and CT26 cells were assessed. The interaction of SORt with ß-lactoglobulin (BLG) was studied using different fluorescence techniques, circular dichroism (CD), zeta potential measurements, and docking simulation. The results of infrared (IR), mass, H NMR, and C NMR spectra demonstrated that the drug was produced with high quality, purity, and efficiency. SORt showed potent cytotoxicity against HCT116 and CT26 cells with IC50 of 8.12 and 5.42 µM, respectively. For BLG binding of SORt, the results showed that static quenching was the cause of the high affinity drug-protein interaction. Three-dimensional fluorescence and synchronous spectra indicated that SORt conformation was changed at different levels. CD suggested that the α-helix content remained almost constant in the BLG-SORt complex, whereas random coil content decreased. Zeta potential values of BLG were more positive after binding with SORt, due to electrostatic interactions between BLG and SORt. Thermodynamic parameters confirmed van der Waals and hydrogen bond interactions in the complex formation. Molecular modelling predicted the presence of hydrogen bonds and electrostatic forces in the BLG-SORt system, which was consistent with the experimental results.

Introducing a pyrazolopyrimidine as a multi-tyrosine kinase inhibitor, using multi-QSAR and docking methods.

In cancer disease, which is one of the problems of today's human societies, the expression of some tyrosine kinase receptors that are effective in the growth and proliferation of cancerous cells rises. Therefore, it is essential to develop and propose new drugs to target the receptors. Performing modeling calculations such as QSAR and docking makes the drug discovery process more efficient. Thus, backpropagation artificial neural network was used for multidimensional quantitative structure-activity relationship (QSAR) to identify essential features of pyrazolopyrimidine moiety, responsible for anticancer activity. The statistical parameters of the model show that multi-QSAR has sufficient validity and accuracy. According to the QSAR modeling, among 26 compounds, the interaction of eight candidates with EGFR, FGFR4, PDGFRA, and VEGFR2 was analyzed by docking modeling. The results showed that 1u compound binds to proteins in a more appropriate area (except FGFR4) with acceptable energy. The results of docking for VEGFR2 binding showed that 1u binds to the active site and binding site of receptor, and it was in the interaction with ten residues in the sites. Although the binding site of 1u molecule in the FGFR4 was not suitable, the binding free energy was excellent (- 9.22 kcal mol-1), which was less than those two anticancer drugs of gefitinib and regorafenib. Furthermore, the values of binding free energy were - 8.69, - 9.64, and - 9.19 kcal mol-1 for EGFR, PDGFRA, and VEGFR2, respectively. Therefore, this study introduces 1u as an anticancer agent that can inhibit the tyrosine kinase receptors.

Probing the Strength and Mechanism of Binding Between Amifampridine and Calf Thymus DNA.

In this work, we have investigated the strength and mechanism of amifampridine (3,4-Diaminopyridine/3,4-DAP) interaction with calf thymus DNA (ct-DNA). The existence and the strength of interaction are evaluated using circular dichroism (CD), UV-vis absorption, and differential pulse voltammogram studies. Results from UV-vis absorption technique indicate that amifampridine can significantly interact with DNA through a binding constant of Kb = 1.66 × 105 M-1 at 298 K. The mechanism of the interaction between amifampridine and DNA is also studied using ionic effect investigations, competitive fluorescence experiments, viscosity measurements, and molecular docking studies. The viscosity results indicate that amifampridine can bind to DNA via intercalation binding mode. Competitive fluorescence experiments using Acridine Orange (AO) and Hoechst 33258 (HO) probes also reveal that amifampridine binds to DNA via an intercalation mode of binding. Finally, the molecular docking studies also suggest that amifampridine tends to bind with the G-C rich region of DNA.

Synthesis of 1-(α-aminoalkyl)-2-naphthol and α-aminonitrile derivatives with molybdenum Schiff base complex covalently bonded on silica-coated magnetic nanoparticles and DNA interaction study of one type of derivatives using computational and spectroscopic methods.

An air- and moisture-stable molybdenum Schiff base complexes immobilized on magnetic iron oxide nanoparticles with a core-shell structure was developed for utilization as a new heterogeneous catalyst. The surface, structural and magnetic characteristics of the nanomaterials were characterized by using Fourier transform infrared (FT-IR) spectroscopy, X-ray powder diffraction (XRD), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and inductively coupled plasma atomic emission spectroscopy (ICP-AES). In application point of view, an ultrasonic assisted one-pot multicomponent protocol for the synthesis of 1-(α-aminoalkyl)-2-naphthol derivatives have been demonstrated under mild condition with short reaction times, high yields and TON values up to 570. To survey the generality of the procedure, we studied the synthesis of α-aminonitrile derivatives with different aldehydes, trimethylsilyl cyanide (TMSCN) and aniline under the same conditions. Additionally, binding interaction of 1-(phenyl(pyridin-2-ylamino)methyl)naphthalen-2-ol (AMAN-1) with various types of rigid DNA and HSA has been investigated by molecular modeling study. In vitro studies under physiological conditions showed that the desired derivative interacts with calf-thymus DNA (ct-DNA) via an intercalative binding mode.

Preparation of a highly stable drug carrier by efficient immobilization of human serum albumin (HSA) on drug-loaded magnetic iron oxide nanoparticles.

Albumin immobilized nanoparticles are known to be biodegradable, easy to prepare and reproducible for drug delivery systems. In summary, we have synthesized a new drug carrier using modified iron oxide nanoparticles. The synthesized drug carrier was characterized by X-ray powder diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FT-IR), vibrating sample magnetometry (VSM) and energy-dispersive X-ray spectroscopy (EDX). Three different drugs were loaded on the modified iron oxide nanoparticles and then human serum albumin (HSA) immobilized on the iron oxide nanoparticles. In addition, the in-vitro antiproliferative activity of Fe3O4@SiO2@Nev@HSA nanoparticles against Hela cancer cell line using MTT colourimetric assay was compared with nevirapine. The results show that Fe3O4@SiO2@Nev@HSA nanoparticles in comparison to nevirapine itself have more effective antiproliferative activity on Hela cancer cell lines. The IC50 value for Fe3O4@SiO2@Nev@HSA nanoparticles was 59.20 µg/ml, which is close to the antiproliferative activity of anti-cancer gefitinib with IC50 value of 76.24 µg/ml. Moreover, in vitro calf thymus DNA (ct-DNA) binding studies were investigated by various spectroscopy techniques.