New bi-phosphonate derivative: Synthesis, characterization, antioxidant activity in vitro and via cyclic voltammetry mode and evaluation of its inhibition of SARS-CoV-2 main protease.

In this study, we have synthesized a new molecule labeled HBPA. Its molecular structure was determined by spectroscopic methods such as: FT-IR, NMR (1H, 13C and 31P); our compound is subjected to two antioxidant activities assays: DPPH scavenging and ferric reducing antioxidant power (FRAP); in the results, HBPA was expanded remarkable inhibition when compared especially to standard BHT with values of 14.936±0.808 and 7.1486±0.0645 µg/ml, respectively; in addition to the scavenging test of superoxide anion integrated in electrochemical process, it elucidated a strongly stable interaction towards the radical by evaluating the thermodynamic descriptors (Gibbs free energy ΔG° and the binding constant Kb). Besides, the electrochemical behavior of HBPA was distinguished by an irreversible system and for the electrochemical regime adopted at the surface of the electrode; a diffusion governed by a slow charge transfer was deduced. The molecular docking of HBPA was conducted beside Chloroquine and the obtained results were indicated a significant binding with active sites of the SARS-CoV-2 main protease (Mpro).

New bi-phosphonate derivative: Synthesis, characterization, antioxidant activity in vitro and via cyclic voltammetry mode and evaluation of its inhibition of SARS-CoV-2 main protease

In this study, we have synthesized a new molecule labeled HBPA. Its molecular structure was determined by spectroscopic methods such as: FT-IR, NMR (1H, 13C and 31P);our compound is subjected to two antioxidant activities assays: DPPH scavenging and ferric reducing antioxidant power (FRAP);in the results, HBPA was expanded remarkable inhibition when compared especially to standard BHT with values of 14.936±0.808 and 7.1486±0.0645 μg/ml, respectively;in addition to the scavenging test of superoxide anion integrated in electrochemical process, it elucidated a strongly stable interaction towards the radical by evaluating the thermodynamic descriptors (Gibbs free energy ΔG° and the binding constant Kb). Besides, the electrochemical behavior of HBPA was distinguished by an irreversible system and for the electrochemical regime adopted at the surface of the electrode;a diffusion governed by a slow charge transfer was deduced. The molecular docking of HBPA was conducted beside Chloroquine and the obtained results were indicated a significant binding with active sites of the SARS-CoV-2 main protease (Mpro). Graphical Image, graphical

New aromatic hydrazones: Synthesis, structural analysis, DFT study, biological activity, ADME-T properties and in silico evaluation of their inhibition of SAS-CoV-2 main protease

Three new hydrazones namely: (2E)-1-(4-methylphenyl-2-[(thiophen-2-yl)methylidene]hydrazine (HZ-1), (2E)-1-(4-methylphenyl)-2-[(thiophen-3yl)methylidene]hydrazine (HZ-2) and (1E)-1[(furan-2-yl)methylidene]-2-(4methylphenyl)hydrazine (HZ-3) have been synthesized by reacting (4-methylphenyl)hydrazine with three heterocyclic aldehydes: 2-thiophenecarboxaldehyde, 3-thiophenecarboxaldehyde and 2-furaldehyde in ethanol at reflux 78°C. The structures of these compounds were confirmed by spectroscopic and physicochemical methods such as UV-Vis, IR, melting point, 1H NMR and 13C NMR spectra. Their antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC and phenanthroline assays. The obtained results indicate that the title molecules exhibit excellent activity better and comparable as standards BHT, BHA and ascorbic acid. Also, the synthesized compounds show a good antibacterial activity against two such: P. aeruginosa and B. subtilis. In addition, the density functional theory (DFT) is used to calculate the optimized molecular structures, electronic and vibrational spectra, reactivity, stability and some quantum chemical parameters of the synthesized molecules. The obtained theoretical results are in good agreement with the experimental results. Finally, in silico predictions of ADME-T and pharmacokinetic parameters indicated that these compounds should have good oral bioavailability. Also, the molecular docking has been used to predict the inhibitory activity of SARS-CoV-2 main protease (Mpro) of the studied hydrazones.

New thiophene-derived α-aminophosphonic acids: Synthesis under microwave irradiations, antioxidant and antifungal activities, DFT investigations and SARS-CoV-2 main protease inhibition

Four new α-aminophosphonic acids containing thiophene ring have been synthesized using simple, neat and catalyst-free conditions, more convenient and eco-friendly method under microwave irradiations. The structures of the title molecules have been confirmed by UV-Vis, FT-IR, 1H NMR, 13C NMR and 31P NMR. Moreover, their antioxidant activity was evaluated using DPPH, ABTS and phenantroline methods;the obtained results indicate that the title molecules exhibit excellent activity better than standards BHT and BHA. Also, the synthesized compounds show a good antifungal activity against two fungi, Fusarium oxysporum and Alternaria alternata. In addition, molecular, electronic properties, stability and reactivity of the synthesized products were studied by the density functional theory (DFT). Furthermore, molecular docking investigations of the studied α-aminophosphonic acids showed a good inhibition of SARS-CoV-2 main protease (Mpro). Graphical Image, graphical .

Novel α-aminophosphonate derivates synthesis, theoretical calculation, Molecular docking, and in silico prediction of potential inhibition of SARS-CoV-2.

Using the Density Functional Theory approach and in silico docking, the current study analyzes the inhibitory role of a novel α-aminophosphonate derivative against SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. FT-IR, UV-Vis, and NMR (1H, 13C, 31P) approaches were used to produce and confirm the novel α-aminophosphonate derivative. The quantum chemical parameters were detremined, and the reactivity of the synthesized molecule was discussed using DFT at the B3LYP/6-31G(d,p) level. In addition, the inhibitory function of the investigated derivative for SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) was estimated using in silico docking. These discoveries could pave the way for novel SARS-CoV-2 therapies to develop and be tested.

Novel α-aminophosphonate derivates synthesis, theoretical calculation, Molecular docking, and in silico prediction of potential inhibition of SARS-CoV-2

Using the Density Functional Theory approach and in silico docking, the current study analyzes the inhibitory role of a novel α-aminophosphonate derivative against SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) of SARS-CoV-2. FT-IR, UV-Vis, and NMR (1H, 13C, 31P) approaches were used to produce and confirm the novel α-aminophosphonate derivative. The quantum chemical parameters were detremined, and the reactivity of the synthesized molecule was discussed using DFT at the B3LYP/6-31G(d,p) level. In addition, the inhibitory function of the investigated derivative for SARS-CoV-2 major protease (Mpro) and RNA dependent RNA polymerase (RdRp) was estimated using in silico docking. These discoveries could pave the way for novel SARS-CoV-2 therapies to develop and be tested. Graphical Image, graphical

Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones.

Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV-Vis, IR, 1H NMR, 13C NMR, 15N NMR and melting point determination. Optimized molecular structures, UV-Vis and IR spectra modeling, the reactivity, the stability and some quantum chemical parameters of the synthesized molecules were modeled utilizing density functional theory (DFT). The obtained theoretical results were found in good agreement with the experimental results. On the other hand, the antioxidant and antibacterial activities of the molecules under study were evaluated to better understand the associated mechanisms of action specifically. Also, predicted ADME-T and pharmacokinetic parameters indicated that these compounds showed good oral bioavailability. Finally, molecular docking has been used to predict the inhibitory activity of the studied hydrazone derivatives on the SARS-CoV-2 main protease (Mpro).

New Phosphinic and Phosphonic acids: Synthesis, antidiabetic, anti-Alzheimer, antioxidant activity, DFT study and SARS-CoV-2 inhibition

Two new α-aminophosphinic (A) and α-aminophosphonic (B) acids were synthesized through a one-pot three-component reaction with good yields of 89 % and 85 %, respectively. The NMR and mass spectroscopies have been used to identify the obtained compounds and confirm their structures, while the IR spectroscopy has been used to characterize functional groups and the type of vibrations involved for the studied compounds. Moreover, the examination of the structural properties and the comparison between the theoretical and the experimental results have been performed using DFT/B3LYP/6-31G (d,p) method. Consequently, the calculated values of the total energy and the energy gap indicate that the (B) is more stable and less reactive than the (A). Also, MEP maps show that oxygen atoms are the probable sites of electrophilic reactions. In this context, the high reactivity of the (A) can be related to the replacement of the (OH) functional group by a hydrogen atom. Further, six in vitro assays have been used to evaluate the antioxidant potential of (A) and (B), which illustrate that both compounds exhibited an excellent activity (e.g., DPPH/IC50(B): 2.42 μg/mL and DPPH/IC50(A): 2.10 μg /mL). The anti-Alzheimer and antidiabetic effects of the studied compounds have been estimated in vitro by evaluating their inhibition of acetylcholinesterase, butyrylcholinesterase and α-glucosidase. The both compounds showed a good inhibitory activity for α-glucosidase (IC50(A): 12.63 and IC50(B): 25.26 μg/mL), and exhibited higher inhibitory activity against butyrylcholinesterase (BChE) than against acetylcholinesterase (AChE) (IC50(A): 36.71±0.95 and IC50(B): 26.56±1.32 μg/mL). Furthermore, the in silico docking study of the inhibitory action of SARS-CoV-2 main protease (Mpro) showed that (A) and (B) have a significant inhibitory action with total energy values of - 96.23 and - 99.99 kcal/mol, respectively.

New bis hydrazone: Synthesis, X-ray crystal structure, DFT computations, conformational study and in silico study of the inhibition activity of SARS-CoV-2.

The aim of this work was to synthesize new bis hydrazone derived from benzil in good yield, namely: (1Z,2Z)-1,2-bis (3-Chlorophenyl Hydrazino) Benzil, encoded by 3-Cl BHB. The benzil (or 1,2-diphenyl ethanedione) reacts with 3-Cl phenyl hydrazine by reflux method using ethanol as solvent to obtain the target compound. The obtained product is depicted by UV-Vis, IR spectroscopy and XRD-crystals analysis. All various contacts intra and intermolecular found in 3-Cl BHB were determined by the X-ray diffraction technique performed on single crystals. On the other hand, the optimized geometric structure of 3-Cl BHB was computed by the DFT/B3LYP method with 6-31 G (d, p) level. So, the bond lengths and angles, frontier molecular orbitals (FMO), surface electrostatic potential of the molecule (MEP), global reactivity descriptors, Mulliken atomic charges, computed vibrational analysis and electronic absorption spectrum were determined to get a good understanding of the electronic properties and the active sites of 3-Cl BHB, then to compare them with experimental data. Additionally, a conformational study was carried out using the same method (DFT). The structure-activity relationships established through molecular docking studies showed that 3-Cl BHB structure strongly binds to the receptors Mpro (-8.90 Kcal/mol) and RdRp (-8.60 Kcal/mol) which confirm its inhibition activity against COVID-19.

New thiophene-derived α-aminophosphonic acids: Synthesis under microwave irradiations, antioxidant and antifungal activities, DFT investigations and SARS-CoV-2 main protease inhibition.

Four new α-aminophosphonic acids containing thiophene ring have been synthesized using simple, neat and catalyst-free conditions, more convenient and eco-friendly method under microwave irradiations. The structures of the title molecules have been confirmed by UV-Vis, FT-IR, 1H NMR, 13C NMR and 31P NMR. Moreover, their antioxidant activity was evaluated using DPPH, ABTS and phenantroline methods; the obtained results indicate that the title molecules exhibit excellent activity better than standards BHT and BHA. Also, the synthesized compounds show a good antifungal activity against two fungi, Fusarium oxysporum and Alternaria alternata. In addition, molecular, electronic properties, stability and reactivity of the synthesized products were studied by the density functional theory (DFT). Furthermore, molecular docking investigations of the studied α-aminophosphonic acids showed a good inhibition of SARS-CoV-2 main protease (Mpro).

New α-Hydrazinophosphonic acid: Synthesis, characterization, DFT study and in silico prediction of its potential inhibition of SARS-CoV-2 main protease.

A new α-Hydrazinophosphonic acid (HDZPA) has been synthesized and its molecular structure was determined using spectroscopic methods. The Density Functional Theory (DFT) at the B3LYP/6-31 G (d,p) level was utilized to determine the electronic properties, vibrational modes and active sites of the examined molecule. In this context, some quantum chemical parameters have been calculated in order to discuss the reactivity of the studied molecule. Also, the inhibition activity of the investigated α-Hydrazinophosphonic acid for SARS-CoV-2 main protease (Mpro) and RNA dependent RNA polymerase (RdRp) has been predicted using in silico docking.