Experimental investigation and molecular simulations of quinone related compounds as COX/LOX inhibitors.

Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer.

Fabrication and Characterization of Silver Nanoparticle-Doped Chitosan/Carboxymethyl Cellulose Nanocomposites for Optoelectronic and Biological Applications.

The synthesis of nanoparticles using environmentally friendly methods for applications in fields such as food packaging and biomedicine has been gaining increasing attention. Organic-inorganic nanostructures offer opportunities to create innovative materials suitable for use in optoelectronics and biological applications. In this study, we focused on producing nanocomposite films by blending carboxymethyl cellulose (CMC) and chitosan (CS) polymers in equal proportions (50/50 wt %) and adding silver nanoparticles (Ag NPs) through a solution casting process.

The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition.

Background: The liver serves as a metabolic hub within the human body, playing a crucial role in various essential functions, such as detoxification, nutrient metabolism, and hormone regulation. Therefore, protecting the liver against endogenous and exogenous insults has become a primary focus in medical research. Consequently, the potential hepatoprotective properties of multiple 4-phenyltetrahydroquinolines inspired us to thoroughly study the influence of four specially designed and synthesized derivatives on carbon tetrachloride (CCl4)-induced liver injury in rats.

The first-in-class pyrazole-based dual InhA-VEGFR inhibitors towards integrated antitubercular host-directed therapy.

Several facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhibitors thematic scaffold.

Structure Modification Converts the Hepatotoxic Tacrine into Novel Hepatoprotective Analogs.

The liver is responsible for critical functions such as metabolism, secretion, storage, detoxification, and the excretion of various compounds. However, there is currently no approved drug treatment for liver fibrosis. Hence, this study aimed to explore the potential hepatoprotective effects of chlorinated and nonchlorinated 4-phenyl-tetrahydroquinoline derivatives.

Synthesis, characterization, and evaluation of polymeric surfactants derived from PET plastic waste as green corrosion inhibitor of steel surfaces in marine environment for heavy industry.

The aim of this work was to prepare a nonionic polymeric surfactant from a recycled product of poly(ethylene terephthalate) plastic waste, PET. In this respect, PET waste was subjected to reverse polymerization (depolymerization) reaction with both ethylene diamine (EDA) in the presence of a catalyst and propylene glycol (PG) in the presence of a transesterification catalyst. The corresponding products obtained were poly amino amide (PETAA) and poly glycol ester (PETPG), respectively.

The Role of Pyrazolo[3,4-d]pyrimidine-Based Kinase Inhibitors in The Attenuation of CCl-Induced Liver Fibrosis in Rats.

Liver Fibrosis can be life-threatening if left untreated as it may lead to serious, incurable complications. The common therapeutic approach is to reverse the fibrosis while the intervention is still applicable. Celecoxib was shown to exhibit some antifibrotic properties in the induced fibrotic liver in rats.

Molecular Mechanics Simulations and Experimental Investigation of the Effect of Tadalafil on Various Inflammatory Pain Mediators.

Purpose: Tadalafil's exact analgesic mechanism is still unclear. The current study aimed to elucidate this mechanism in an inflammatory pain model.

Methods: Computer-assisted simulation docking experiments were carried out to assess the binding of tadalafil to different ligands.

New pyrazolylpyrazoline derivatives as dual acting antimalarial-antileishamanial agents: synthesis, biological evaluation and molecular modelling simulations.

Promising inhibitory activities of the parasite multiplication were obtained upon evaluation of antimalarial activities of new pyrazolylpyrazoline derivatives against infected mice. Further evaluation of and against chloroquine-resistant strain (RKL9) of showed higher potency than chloroquine. antileishmanial activity testing against promastigote and amastigote forms indicated that , and possessed promising activity compared to miltefosine and amphotericin B deoxycholate.

Structure-guided approach on the role of substitution on amide-linked bipyrazoles and its effect on their anti-inflammatory activity.

A structure-guided modelling approach using COX-2 as a template was used to investigate the effect of replacing the chloro atom located at the chlorophenyl ring of amide-linked bipyrazole moieties, aiming at attaining better anti-inflammatory effect with a good safety profile. Bromo, fluoro, nitro, and methyl groups were revealed to be ideal candidates. Consequently, new bipyrazole derivatives were synthesised.

Halting colorectal cancer metastasis via novel dual nanomolar MMP-9/MAO-A quinoxaline-based inhibitors; design, synthesis, and evaluation.

Matrix metalloproteinase-9 (MMP-9) and monoamine oxidase-A (MAO-A) are central signaling nodes in CRC and promotors of distant metastasis associated with high mortality rates. Novel series of quinoxaline-based dual MMP-9/MAO-A inhibitors were synthesized to suppress CRC progression. The design rationale combines the thematic pharmacophoric features of MMP-9 and MAO-A inhibitors in hybrid scaffolds.

Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis.

We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their ICs, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity.

Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines.

The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines.

Targeting multiple conformations of SARS-CoV2 Papain-Like Protease for drug repositioning: An in-silico study.

Papain-Like Protease (PLpro) is a key protein for SARS-CoV-2 viral replication which is the cause of the emerging COVID-19 pandemic. Targeting PLpro can suppress viral replication and provide treatment options for COVID-19. Due to the dynamic nature of its binding site loop, PLpro multiple conformations were generated through a long-range 1 micro-second molecular dynamics (MD) simulation.

Design, synthesis, biological evaluation and in silico studies of certain aryl sulfonyl hydrazones conjugated with 1,3-diaryl pyrazoles as potent metallo-β-lactamase inhibitors.

Based on a structure-guided approach, aryl sulfonyl hydrazones conjugated with 1,3-diaryl pyrazoles were designed to target metallo-β-lactamases (MBLs), using Klebsiella pneumoniaeNDM-1 as a model. The in vitro MBLs inhibition showed remarkable inhibition constant for most of the designed compounds at a low micromolar range (1.5-16.

Synthesis, biological evaluation and modeling of hybrids from tetrahydro-1H-pyrazolo[3,4-b]quinolines as dual cholinestrase and COX-2 inhibitors.

New tetrahydro-1H-pyrazolo[3,4-b]quinoline derivatives were designed, synthesized and characterized as dual anticholinestrase and cyclooxygenase-2 inhibitors. The in vitro and in vivo anti-cholinesterase evaluation exhibited promising activities with lower hepatotoxicity for many candidates compared to tacrine as a reference. Furthermore, their anti-inflammatory activity using in vitro (COX-1/COX-2) inhibitory assay demonstrated superior activity to celecoxib with higher selectivity indices for some compounds.

Chlorinated tacrine analogs: Design, synthesis and biological evaluation of their anti-cholinesterase activity as potential treatment for Alzheimer's disease.

In search of potent acetyl cholinesterase inhibitors with low hepatotoxicity for the treatment of Alzheimer's disease, introduction of a chloro substitution to tacrine and some of its analogs has proven to be beneficial in maintaining or potentiating the cholinesterase inhibitory activity. Furthermore, it was found to be able to reduce the hepatotoxicity of the synthesized compounds, which is the main target of the study. Accordingly, a series of new 4-(chlorophenyl)tetrahydroquinoline derivatives, was synthesized and characterized.

Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals.

Purpose: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes' elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities.

Synthesis of new pyrazolo[3,4-d]pyrimidine derivatives and evaluation of their anti-inflammatory and anticancer activities.

This study reports the synthesis of two series of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to piperazine moiety through different amide linkages. The newly synthesized compounds were evaluated for anticancer activity against four cell lines (MDA-MB-231, MCF-7, SF-268, B16F-10) and cyclooxygenase (COX-2) protein expression inhibition in lipopolysaccharide (LPS)-activated rat monocytes. The results revealed that most of the synthesized compounds showed moderate-to-high cytotoxic activity against at least one cell line, with compound 10b being the most active against all used cell lines (IC values 5.

Compounds Containing Azole Scaffolds as Cyclooxygenase Inhibitors: A Review.

There has been considerable interest in azole-containing compounds as promising antiinflammatory agents. Designed compounds with five-membered nitrogen-containing nuclei have demonstrated good anti-inflammatory activity, indicating their potential for the treatment of this highly irritating condition. Pyrazoles, have attracted much more attention than other azoles, however, reports on other azoles demonstrated that they were as effective as pyrazoles.

Synthesis of some new amide-linked bipyrazoles and their evaluation as anti-inflammatory and analgesic agents.

Four series of new bipyrazoles comprising the N-phenylpyrazole scaffold linked to polysubstituted pyrazoles or to antipyrine moiety through different amide linkages were synthesized. The synthesized compounds were evaluated for their anti-inflammatory and analgesic activities. In vitro COX-1/COX-2 inhibition study revealed that compound 16b possessed the lowest IC50 value against both COX-1 and COX-2.

Design, synthesis and antimicrobial evaluation of methyl pyridyl-2,4- dioxobutanoates and some new derived ring systems.

This work describes the synthesis of new series of compounds derived from methyl pyridyl- 2,4-dioxobutanoates that contain pyridine ring attached to substituted bioactive heterocyclic moieties in order to investigate their preliminary in vitro antibacterial and antifungal activities. The results revealed that most of the tested compounds exhibited significant activity against P. aeruginosa.

Design, synthesis and biological screening of some pyridinylpyrazole and pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic, antipyretic and antimicrobial agents.

A series of substituted pyridinylpyrazole (or isoxazole) derivatives were synthesized and evaluated for their anti-inflammatory (AI) activity using formalin-induced paw edema bioassays. Their inhibitory activities of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The analgesic activity of the same compounds was evaluated using rat-tail withdrawal technique.

Aryloxyethylamines: binding at alpha7 nicotinic acetylcholine receptors.

Structure-affinity relationships for the binding of 3-[2-(N,N,N-trimethylammonium)ethoxy]pyridine (AXPQ) at alpha7 nACh receptors were investigated due to its close structural similarity to a known alpha7 antagonist.