Evaluation of Quinazolin-2,4-Dione Derivatives as Promising Antibacterial Agents: Synthesis, In Vitro, In Silico ADMET and Molecular Docking Approaches.

A series of new quinazolin-2,4-dione derivatives incorporating amide/eight-membered nitrogen-heterocycles -, in addition, acylthiourea/amide/dithiolan-4-one and/or phenylthiazolidin-4-one - and -. The starting compound was prepared by reaction of 4-(2,4-dioxo-1,4-dihydro-2-quinazolin-3-yl)-benzoyl chloride with ammonium thiocyanate and cyanoacetic acid hydrazide. The reaction of with strong electrophiles, namely, -aminophenol, -amino thiophenol, and/or -phenylene diamine, resulted in corresponding quinazolin-2,4-dione derivatives incorporating eight-membered nitrogen-heterocycles -.

Synthesis, crystal structure, Hirshfeld surface analysis, and DFT calculation of 4-(5-(((1-(3,4,5-trimethoxyphenyl)-1-1,2,3-triazol-4-yl)methyl)thio)-4-phenyl-4-1,2,4-triazol-3-yl)pyridine.

Triazole is considered as a privileged scaffold in medicinal chemistry by virtue of it is diverse biological activity. several drugs currently in the market possess triazole moiety. In this study click chemistry was performed on the pyridine based 1,2,4-triazole-tethered propargyl moiety to afford 4-(5-(((1-(3,4,5-trimethoxyphenyl)-1-1,2,3-triazol-4-yl)methyl)thio)-4-phenyl-4-1,2,4-triazol-3-yl)pyridine The new compound was fully characterized by H NMR, C NMR, HRMS and X-ray diffraction (XRD).

New 1,3-diphenyl-1-pyrazol-5-ols as anti-methicillin resistant agents: Synthesis, antimicrobial evaluation and studies.

In the present work, two hybrid series of pyrazole-clubbed pyrimidine and pyrazole-clubbed thiazole compounds from 4-acetyl-1,3-diphenyl-1-pyrazole-5(4)-ole were synthesized as novel antimicrobial agents. Their chemical structures were thoroughly elucidated in terms of spectral analyses such as IR, H NMR, C NMR and mass spectra. The compounds were evaluated for their antimicrobial efficiency against various standard pathogen strains, gram -ive bacteria (, ), gram + ive bacteria (MRSA, ), and Unicellular fungi () microorganisms.

Antimicrobial Potency and β-Carbonic Anhydrase Inhibition Efficacy of Phenazone-Based Molecules.

In this investigation, 4-antipyrinecarboxaldhyde was reacted with methyl hydrazinecarbodithioate to afford the carbodithioate derivative . The as-prepared carbodithioate derivative is considered to be a key molecule for the preparation of new antipyrine-1,3,4-thiadiazole-based molecules (-) through its reaction with the appropriate hydrazonoyl halides. Furthermore, a typical Biginelli three-component cyclocondensation reaction involving ethyl acetoacetate, 4-antipyrinecarboxaldhyde, and thiourea under the standard conditions is carried out in the presence of sulfuric acid to afford the corresponding antipyrine-pyrimidine hybrid molecule ().

β-Cyclodextrin-Functionalized FeO-Supported Pd-Nanocatalyst for the Reduction of Nitroarenes in Water at Mild Conditions.

In this study, a novel heterogeneous catalyst (FeO@β-CD@Pd) has been developed by the deposition of palladium nanoparticles on the β-cyclodextrin-functionalized surface of magnetic FeO. The catalyst was prepared by a simple chemical co-precipitation method and characterized extensively by using Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-optical emission spectrometry (ICP-OES) analyses. Herein, the applicability of the prepared material was evaluated for the catalytic reduction of environmentally toxic nitroarenes to the corresponding anilines.

Modified Graphite Pencil Electrode Based on Graphene Oxide-Modified FeO for Ferrocene-Mediated Electrochemical Detection of Hemoglobin.

This study describes the synthesis of graphene oxide-modified magnetite (rGO/FeO) and its use as an electrochemical sensor for the quantitative detection of hemoglobin (Hb). rGO is characterized by a 2θ peak at 10.03° in its X-ray diffraction, 1353 and 1586 cm vibrations in Raman spectroscopy, while scanning electron microscopy coupled with energy-dispersive spectroscopy of rGO and rGO/FeO revealed the presence of microplate structures in both materials and high presence of iron in rGO/FeO with 50 wt %.

Design and biological evaluation of 3-substituted quinazoline-2,4(1,3)-dione derivatives as dual c-Met/VEGFR-2-TK inhibitors.

The dual c-Met/vascular endothelial growth factor receptor 2 (VEGFR-2) TK inhibition is a good strategy to overcome therapeutic resistance to small molecules VEGFR-2 inhibitors. In this study, we designed 3-substituted quinazoline-2,4(1,3)-dione derivatives as dual c-Met/VEGFR-2 TK inhibitors. We introduced new synthetic methods for reported derivatives of 3-substituted quinazoline-2,4(1,3)-dione -, in addition to the preparation of some new derivatives namely, and -.

Newly Synthesized Pyrazolinone Chalcones as Anticancer Agents via Inhibiting the PI3K/Akt/ERK1/2 Signaling Pathway.

A series of novel pyrazolinone chalcones have been synthesized through the condensation of azo pyrazolinone derivatives with various aromatic aldehydes. Spectroscopic techniques and elemental analysis have both corroborated this. Furthermore, all compounds were screened in silico for their ability to inhibit cancer proliferation and metastasis by targeting the PI3K/Akt signaling pathway.

Novel Thiadiazole-Based Molecules as Promising Inhibitors of Black Fungi and Pathogenic Bacteria: In Vitro Antimicrobial Evaluation and Molecular Docking Studies.

Novel 1,3,4-thiadiazole derivatives were synthesized through the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate and the appropriate hydrazonoyl halides in the presence of a few drops of diisopropylethylamine. The chemical structure of the newly fabricated compounds was inferred from their microanalytical and spectral data. With the increase in microbial diseases, fungi remain a devastating threat to human health because of the resistance of microorganisms to antifungal drugs.

Synthesis, Molecular Docking Analysis and Biological Evaluation of Some New Heterocyclic Scaffolds-Based Indole Moiety as Possible Antimicrobial Agents.

In the present study, a general approach for the synthesis of 1-(1-indol-3-yl)-3,3-dimercaptoprop-2-en-1-one and 5-(1-indol-3-yl)-3-1,2-dithiole-3-thione was performed. They are currently used as efficient precursors for the synthesis of some new compounds bearing five- and/or six-membered heterocyclic moieties, e.g.

Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens.

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate () with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using , , , , , and .

An efficient synthesis of furan-3(2)-imine scaffold from alkynones.

A novel efficient method to generate spiro furan-3(2)-imine derivatives is established by the reaction between the ,-unsaturated ketones and aniline derivatives. The reaction involves 1,4- addition of aniline followed by the subsequent intramolecular cyclization mediated by tertiary alcohol to produce the furan-3(2)-imine. All the synthesized compounds are characterized using nuclear magnetic resonance and high-resolution mass spectrometry (HRMS).

Antibacterial Activities and Molecular Docking of Novel Sulfone Biscompound Containing Bioactive 1,2,3-Triazole Moiety.

In this study, a new synthetic 1,2,3-triazole-containing disulfone compound was derived from dapsone. Its chemical structure was confirmed using microchemical and analytical data, and it was tested for its in vitro antibacterial potential. Six different pathogenic bacteria were selected.

Lysozyme and Human Serum Albumin Proteins as Potential Nitric Oxide Cardiovascular Drug Carriers: Theoretical and Experimental Investigation.

Nitric oxide-containing drugs present a critical remedy for cardiovascular diseases. Nitroglycerin (NG, O-NO) and -nitrosoglutathione (SNG, S-NO) are the most common nitric oxide drugs for cardiovascular diseases. Insights regarding the binding affinity of NO drugs with lysozyme and human serum albumin (HSA) proteins and their dissociation mechanism will provide inquisitive information regarding the potential of the proteins as drug carriers.

Synthesis, Anticancer Evaluation, Computer-Aided Docking Studies, and ADMET Prediction of 1,2,3-Triazolyl-Pyridine Hybrids as Human Aurora B Kinase Inhibitors.

A novel series of 1,2,3-triazolyl-pyridine hybrids were prepared through the reaction of the triazole derivative () with the appropriate aldehyde () and malononitrile or ethyl cyanoacetate in the presence of ammonium acetate in refluxed acetic acid. The chemical composition of the products was established on the basis of spectral and elemental analyses. Aurora B kinase is a protein with diverse biological actions in controlling tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, making it an emerging target for diseases such as hepatocellular carcinoma (HCC).

Synthesis, Molecular Docking Screening and Anti-Proliferative Potency Evaluation of Some New Imidazo[2,1-]Thiazole Linked Thiadiazole Conjugates.

Background: Imidazo[2,1-]thiazole scaffolds were reported to possess various pharmaceutical activities.

Results: The novel compound named methyl-2-(1-(3-methyl-6-(-tolyl)imidazo[2,1-]thiazol-2-yl)ethylidene)hydrazine-1-carbodithioate acted as a predecessor molecule for the synthesis of new thiadiazole derivatives incorporating imidazo[2,1-]thiazole moiety. The reaction of with the appropriate hydrazonoyl halide derivatives - and - had produced the respective 1,3,4-thiadiazole derivatives - and -.

Divergent Strategy for Diastereocontrolled Synthesis of Small- and Medium-Ring Architectures.

Nitrogen and oxygen medium rings, in particular nine-membered rings, epitomize a unique area of chemical space that occurs in many natural products and biologically appealing compounds. The scarcity of 8- to 12-membered rings among clinically approved drugs is indicative of the difficulties associated with their synthesis, principally owing to the unfavorable entropy and transannular strain. We report here a scandium triflate-catalyzed reaction that allows for a modular access to a diverse collection of nine-membered ring heterocycles in a one-pot cascade and with complete diastereocontrol.

Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes.

Four new complexes derived from adamantly containing hydrazone () ligand with Cu(II) (), Co(II) (), Ni(II) () and Zn(II) (), have been synthesized and characterized using different physicochemical methods. The structure of the ligand and its copper complex have been established by single-crystal X-ray diffraction direct methods, which reveal that complex has distorted square-pyramidal geometry. Complexes - are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities.

Homology Modeling and Virtual Screening Studies of Antigen MLAA-42 Protein: Identification of Novel Drug Candidates against Leukemia-An Approach.

Monocytic leukemia-associated antigen-42 (MLAA-42) is associated with excessive cell division and progression of leukemia. Thus, human MLAA-42 is considered as a promising target for designing of new lead molecules for leukemia treatment. Herein, the 3D model of the target was generated by homology modeling technique.

Active site prediction for comparative model structures with thematics.

THEMATICS (Theoretical Microscopic Titration Curves) is a simple, reliable computational predictor of the active sites of enzymes from structure. Our method, based on well-established Finite Difference Poisson-Boltzmann techniques, identifies the ionisable residues with anomalous predicted titration behavior. A cluster of two or more such perturbed residues is a very reliable predictor of the active site.

Future directions in protein function prediction.

New directions in computational methods for the prediction of protein function are discussed. THEMATICS, a method for the location and characterization of the active sites of enzymes, is featured. THEMATICS, for Theoretical Microscopic Titration Curves, is based on well-established finite-difference Poisson-Boltzmann methods for computing the electric field function of a protein.