Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti- Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating (), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, and adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best inhibitors.

Attenuation of Lipopolysaccharide-Induced Inflammatory Responses through Inhibition of the NF-κB Pathway and the Increased NRF2 Level by a Flavonol-Enriched -Butanol Fraction from .

Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from () was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E, and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively.

Polyoxygenated Cyclohexenes from with Multi-Enzyme Targeting Properties Relevant in Type 2 Diabetes and Obesity.

Shikimic acid-derived polyoxygenated cyclohexene natural products commonly occurring in several species of the represent natural products with promising biological activities. While a number of derivatives have been reported from (), further studies are needed to discover additional bioactive congeners, particularly derivatives with multi-protein target inhibitory properties implicated in diseases such as diabetes and obesity. In this paper, isolation and identification of a new highly oxygenated cyclohexene, uvagrandol (), along with the known compound (-)-zeylenone () from the DCM sub-extract of following and assessment of their enzyme inhibitory properties against α-glucosidase, dipeptidyl peptidase IV, porcine lipase, and human recombinant monoacylglycerol lipase are reported.

Antiproliferative and Cytotoxic Cytochalasins from Inhibit Actin Polymerization and Aggregation.

Laying the groundwork on preliminary structure-activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, . A new cytochalasan analog triseptatin (), along with the previously described cytochalasans deoxaphomin B () and cytochalasin B (), and polyketide derivatives -4-hydroxy-6-deoxyscytalone () and 6-hydroxymellein () were isolated from the rice culture of . The structure of was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS).

COX Inhibitory and Cytotoxic Naphthoketal-Bearing Polyketides from .

Axenic fermentation on solid rice of the saprobic fungus afforded two new highly oxidized naphthalenoid polyketide derivatives, sparticatechol A () and sparticolin H () along with sparticolin A (). The structures of and were elucidated on the basis of their NMR and HR-ESIMS spectroscopic data. Assignment of absolute configurations was performed using electronic circular dichroism (ECD) experiments and Time-Dependent Density Functional Theory (TDDFT) calculations.

Anti-HIV reverse transcriptase plant polyphenolic natural products with in silico inhibitory properties on seven non-structural proteins vital in SARS-CoV-2 pathogenesis.

Background: Accessing COVID-19 vaccines is a challenge despite successful clinical trials. This burdens the COVID-19 treatment gap, thereby requiring accelerated discovery of anti-SARS-CoV-2 agents. This study explored the potential of anti-HIV reverse transcriptase (RT) phytochemicals as inhibitors of SARS-CoV-2 non-structural proteins (nsps) by targeting in silico key sites in the structures of SARS-CoV-2 nsps.

Catechol-Bearing Polyketide Derivatives from .

Sparticols A () and B (), two catechol-bearing naphthalenedioxy derivatives, were isolated from the submerged culture of the Spanish broom inhabiting Dothideomycetes fungus, The structures of and were established by NMR spectroscopic analysis and high-resolution mass spectrometry. The 8 absolute configuration of their β-hydroxy functionalities was determined by ECD-TDDFT. Both compounds exhibited inhibitory activity against with an MIC value of 66.

Virtual screening-driven drug discovery of SARS-CoV2 enzyme inhibitors targeting viral attachment, replication, post-translational modification and host immunity evasion infection mechanisms.

The novel coronavirus SARS-CoV2, the causative agent of the pandemic disease COVID-19, emerged in December 2019 forcing lockdown of communities in many countries. The absence of specific drugs and vaccines, the rapid transmission of the virus, and the increasing number of deaths worldwide necessitated the discovery of new substances for anti-COVID-19 drug development. With the aid of bioinformatics and computational modelling, ninety seven antiviral secondary metabolites from fungi were docked onto five SARS-CoV2 enzymes involved in viral attachment, replication, post-translational modification, and host immunity evasion infection mechanisms followed by molecular dynamics simulation and ADMET prediction (absorption, distribution, metabolism, excretion and toxicity) of the hit compounds.

Enhanced Oral Bioavailability of the Pharmacologically Active Lignin Magnolol via Zr-Based Metal Organic Framework Impregnation.

Bioavailability plays an important role in drug activity in the human body, as certain drug amounts should be present to elicit activity. However, low bioavailability of drugs leads to negligible use for human benefit. In this study, the diversely active neolignan, magnolol, was impregnated onto a Zr-based organometallic framework [Uio-66(Zr)] to increase its low bioavailability (4-5%) and to test its potential acute oral toxicity.

Alpha-Glucosidase- and Lipase-Inhibitory Phenalenones from a New Species of Originating from Thailand.

The alpha-glucosidase- and lipase-inhibitory activities of three phenalenones (-) and one phenylpropanoid () from the ethyl acetate extracts of a sp. are described. They represent the first secondary metabolites reported from the genus .