Synthesis of new quinoline scaffolds via a solvent-free fusion method and their anti-microbial properties

Purpose: To develop a robust and simple fusion-based methodology for the synthesis of various 5-(-3- nitrophenyl) pyrimido[5,4-c] quinoline-2,4(1H,3H)-diones (5 – 9).Method: The synthesis involved formation of a Knoevenagel product using barbituric acid and 3- nitrobenzaldehyde which cyclized on fusing with various sulfanilamides in a sealed tube at 170 – 212°C. This resulted in the synthesis of the target quinolines (5 – 9). To evaluate their antibacterial and antiviral properties, the synthesized quinolines were tested against four gram-negative bacterial strains and four poultry viruses. The MIC and IC50 of each active compound were calculated.Results: Data from NMR, mass spectrometry and elemental analysis confirmed the formation of quinoline scaffolds. Antibacterial screening revealed that all the compounds had antibacterial activities. However, the minimum inhibitory concentration (MIC) of compounds 6 – 8 and 9 against Proteus vulgaris and Klebsiella pneumoniae showed that these compounds were more active than the standard drug ampicillin. Antiviral studies and IC50 values showed that compounds 5 – 9 were effective against Newcastle disease virus (NDV) and infectious bursal disease virus (IBDV), while compounds 5, 6 and 8 were active against avian influenza virus subtype H9N2 (AIV); compounds 7 and 8 were active against infectious bronchitis virus (IBV).Conclusion: A simple strategy of fusion of Knoevenagel product with aromatic amines can be used to synthesize highly functionalized quinoline scaffolds which are potential drug candidates for development of new antibacterial and antiviral agents.Keywords: Quinoline scaffolds, Barbituric acid, Knoevenagel condensation, Antiviral, Antibacteria

(±)-4,12,15,18,26-Penta­hydroxy-13,17-dioxahepta­cyclo­[14.10.0.03,14.04,12.06,11.018,26.019,24]hexa­cosa-1,3(14),6(11),7,9,15,19,21,23-nona­ene-5,25-dione monohydrate

The title compound, C24H14O9·H2O, displays a cup-shaped form. The water mol­ecule is disordered over two set of sites with an occupancy ratio of 0.78:0.22. The mol­ecule of the compound has four stereocenters and corresponds to the SSRR/RRSS diastereoisomer. In the mol­ecule, the maximum dihedral angle between the planar benzene rings is 80.40 (4)°. The H atoms of the hy­droxy groups are engaged in hydrogen bonding, forming infinite chains parallel to the a axis. These chains are inter­linked through water mol­ecules, resulting in the formation of a two-dimensional network parallel to the (001) plane. Futhermore C—H⋯O, C—H⋯π and slipped π–π inter­actions result in the formation of a three-dimensional network

Synthesis of novel cyanoacetamides derivatives and their urease inhibition studies

The present study reports a convenient approach for the synthesis of cyanoacetamide based derivatives (7-27) via two-step process involving Knoevenagel reaction, followed by three component reaction to avail desired compounds. All the synthesized compounds were obtained in good to excellent yield and extensively characterized employing 1H NMR, 13C NMR, mass spectrometry and physical parameters. Further, these compounds were screened for urease inhibition. All of the synthesized compounds exhibited good to excellent urease activity notably compound 15 and 19 showed excellent urease inhibition activity with IC50 value ~17.34 μg/mL and 36.75 μg/mL in comparison to thiourea (used as standard) having IC50 value ~27.5 μg/mL

4-{2-[(Z)-(5-Methyl-2-fur­yl)methyl­idene­amino]­eth­yl}benzene­sulfonamide

In the title compound, C14H16N2O3S, the dihedral angle between the phenyl and 5-methyl­furan groups is 54.89 (14)° and the C=N bond assumes a trans conformation. In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) ring motifs. The dimers are inter­linked by N—H⋯N hydrogen bonds, resulting in the formation of infinite chains extending along the b axis. The packing is consolidated by weak C—H⋯π inter­actions

Synthesis, biological evaluation and molecular docking studies of Mannich bases derived from 1, 3, 4-oxadiazole- 2-thiones as potential urease inhibitors

Purpose: To design and synthesize a series of new structural motifs of urease inhibitors, 3-[{(substituted phenyl) amino} methyl]-5-(3, 4, 5-trimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones and 3- {[(pyridin-2-yl)amino]methyl}-5-(3,4,5-trimethoxy phenyl)-1,3,4-oxadiazole-2(3H)-thiones from 1, 3, 4- oxadiazole-2-thione.Methods: Targeted Mannich base derivatives were synthesized by the reaction of 1, 3, 4-oxadiazole-2- thione with formaldehyde and respective aromatic amines. These structural motifs were subjected to 1H–NMR, 13C–NMR and mass spectrometric analysis. Compound 4, i.e., 1,3,4-oxadiazole-2-thione and its corresponding Mannich bases (5-17) were subjected to in silico screening as urease inhibitors, using crystal structure of urease (Protein Data Bank ID: 5FSE) as a model enzyme. Furthermore, the targeted compounds were evaluated for their in vitro urease inhibition and anti-oxidant activities using thiourea and propyl gallate as standards, respectively.Results: The docking score of targeted compounds predicted that they are promising urease inhibitors. Subsequently, in vitro studies on Jack bean urease supported the results from virtual screening, and found compounds 4, 5, 9,10,12, 13, 14 and 15 very potent urease inhibitors with half-maximal inhibitory concentration (IC50) values in the range of 5.93 ± 0.13 to 9.76 ± 0.11, relative to thiourea (IC50 = 21.25 ± 0.15). Compounds 4 – 6, and compounds 12 - 17 also exhibited higher antioxidant activities than propyl gallate.Conclusion: In view of their potent urease inhibition and antioxidant activities, these structural motifs have potentials as new candidates for the development of anti-ulcer drugs.Keywords: 1, 3, 4-Oxadiazole-2-thiones, Antioxidant, Molecular docking, Urease inhibition, Anti-ulce

A Comparative Study of Cerium- and Ytterbium-Based GO/g-C3N4/Fe2O3 Composites for Electrochemical and Photocatalytic Applications

The design of sustainable and efficient materials for efficient energy storage and degradation of environmental pollutants (specifically organic dyes) is a matter of major interest these days. For this purpose, cerium- and ytterbium-based GO/g-C3N4/Fe2O3 composites have been synthesized to explore their properties, especially in charge storage devices such as supercapacitors, and also as photocatalysts for the degradation of carcinogenic dyes from the environment. Physicochemical studies have been carried out using XRD, FTIR, SEM, and BET techniques. Electrochemical techniques (cyclic voltammetry, galvanic charge discharge, and electrochemical impedance spectroscopy) have been employed to measure super-capacitance and EDLC properties. Results show that the gravimetric capacitance calculated from GCD results is 219 Fg−1 for ytterbium- and 169 Fg−1 for cerium-based nanocomposites at the current density of 1 A/g and scan rate of 2 mV/sec. The specific capacitance calculated for the ytterbium-based nanocomposite is 189 Fg−1 as compared to 125 Fg−1 for the cerium-based material. EIS results pointed to an enhanced resistance offered by cerium-based nanocomposites as compared to that of ytterbium, which can be assumed with the difference in particle size, as confirmed from structural studies including XRD. From obtained results, ytterbium oxide-based GO/g-C3N4/Fe2O3 is proven to be a better electro-catalyst as compared to cerium-based nanocomposites. Photocatalytic results are also in agreement with electrochemical results, as the degradation efficiency of ytterbium oxide-based GO/g-C3N4/Fe2O3 (67.11 and 83.50% for rhodamine B and methylene blue dyes) surpasses values observed for cerium-based GO/g-C3N4/Fe2O3 (63.08 and 70.61%)

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms

New Pyrimidinone Bearing Aminomethylenes and Schiff Bases as Potent Antioxidant, Antibacterial, SARS-CoV-2, and COVID-19 Main Protease M Pro Inhibitors: Design, Synthesis, Bioactivities, and Computational Studies

New 2-thioxopyrimidinone derivatives (A1–A10) were synthesized in 87–96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6–A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6–A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand–protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations

N,N\u27-dialkyl-2-thiobarbituric acid based sulfonamides as potential SARS-CoV-2 main protease inhibitors

An efficient methodology was developed to generate novel N,N0-dialkyl-2-thiobarbituric acid based sulfonamides S1–S4 in good to excellent yields 84%–95%. The synthesized compounds S1–S4 were docked to screen their in silico activities against two enzymes i.e., SARS-CoV-2 main protease enzyme with unliganded active site 2019-nCoV, coronavirus disease 2019, COVID-19 PDB ID: 6Y84 and SARS-CoV-2 M PDB ID: 6LU7. Furthermore, some in silico physicochemical and physicokinetic properties were evaluated using the OSIRIS Property Explorer, Molinspiration property calculator, ADMET property calculator, and GUSAR to assess these compounds as potential candidates as lead compounds for the quest of SARS-CoV-2 main protease inhibitors. Molecular docking analyses of the synthesized compounds predicted that compound S3 is more potent as SARS-CoV-2 main protease inhibitor with binding energy –11.65 kcal/mol in comparison with reference inhibitor N3 –10.95 kcal/mol, whereas compounds S1, S2, and S4 recorded comparable binding energies –9.89, –10.84, and –10.94 kcal/mol with reference inhibitor N3, which were much better than remdesivir –9.85 kcal/mol. In case of SARSCoV- 2 M , all compounds S1–S4 with docking energy values of –7.28, –8.38, –8.31, and –7.34 kcal/mol, respectively, were found to be potent in comparison with reference inhibitor N3 –6.31 kcal/mol and remdesivir –6.33 kcal/mol. Ligand efficiency values against the target SARS-CoV-2 proteins, as well as a -glucosidase and DNA-apurinic or apyrimidinic site lyase inhibition results of these newly synthesized compounds, were also found to be promising. pro pr

Hydrothermal synthesis and characterization of lanthanide oxalates: <i style="">In situ</i> oxalate formation from tartaric acid in presence of KI

708-713Two new three-dimensional lanthanide oxalates [Pr2(C2O4)3(H2O)4]·2H2O (1) and [Nd2(C2O4)3(H2O)4]·2H2O (2) and a two-dimensional oxalate [Pr2(C2O4)3(H2O)6]·3H2O (3) have been prepared by hydrothermal process and characterized by single crystal X-ray analysis. Compound (1) crystallizes in monoclinic crystal system with P21/c space group whereas (2) crystallizes in triclinic crystal system with Pī space group. Although Pr and Nd are twin lanthanides, they have produced different crystal structures under the same reaction conditions. Compound (3) is produced by the in situ hydrothermal degradation of tartaric acid to oxalate ions in presence of KI. In this reaction, the iodide anion instead of metal cation, acts as the reducing agent during the degradation of tartaric acid to oxalate. Thermogravimetric, elemental analysis and IR studies have also been carried out for these compounds