Designing Novel InhA Inhibitors for Antituberculosis Agents Using ab Initio Fragment Molecular Orbital Calculations.

Tuberculosis is an ancient chronic disease caused by () and remains one of the leading causes of death worldwide. InhA, an enoyl-ACP reductase in , plays a crucial role in the biosynthesis of mycolic acids, essential constituents of the mycobacterial cell wall. Therefore, InhA enzyme has been considered as a promising target for the development of novel antitubercular drugs.

Design, synthesis, and evaluation of pyrrole-indole hybrids as dual tubulin and aromatase inhibitors with potent anticancer activities.

Twenty-four new pyrrolyl-3-phenyl-1-indole-2-carbohydrazide derivatives were designed, synthesized and evaluated for their anticancer activities and dual inhibition properties against tubulin and aromatase. Their anticancer activities were highly potent against the NCI60 human cancer cell line panel. Amongst them, single chloro-substituted derivative 3h was the strongest tubulin inhibitor, disrupting the microtubule structure by inhibiting the colchicine site, while potently inhibiting aromatase (IC = 1.

Antiproliferative cassaine diterpenoid amines from the leaves and twigs of the traditional Thai medicinal plant Erythrophleum teysmannii (Kurz) Craib.

Ethnopharmacological Relevance: Erythrophleum teysmannii (Kurz) Craib is a medicinal plant used by traditional healers in Laos and Thailand to treat cancer. Despite ethnopharmacological reports about plant extracts from this genus as cancer drug formulae, there is a knowledge gap about the chemical composition and potential pharmacological effects of E. teysmannii.

Hybrid virtual screening identifies dipyrazole carboxamide derivatives as novel direct InhA inhibitors with antitubercular activity.

Direct inhibitors of M. tuberculosis enoyl-acyl carrier protein reductase (M. tuberculosis InhA) remain effective against variants with mutations associated with isoniazid resistance.

A Direct Route to Habiterpenol Synthesis Using Anticopalic Acid as a Chiral Pool Template.

The concise total synthesis of habiterpenol utilizing the highly abundant natural product, anticopalic acid, as a chiral pool starting material is presented in this work. The key synthetic transformations involved the acid-induced cyclization of the bicyclic anticopalic acid to directly construct the C-ring of the habiterpenol framework and the aromatic Nazarov cyclization to afford the pentacyclic ring-fused indane core structure. The synthesis was completed in 10 steps with an overall yield of 17.

In Vitro Development of Local Antiviral Formulations with Potent Virucidal Activity Against SARS-CoV-2 and Influenza Viruses.

This study investigates the in vitro antiviral potential of D-limonene (DLM), monolaurin (ML), and cetylpyridinium chloride (CPC) in formulations targeting SARS-CoV-2 and influenza viruses. The aim was to develop oral and nasal formulations with optimized concentrations of these active ingredients to evaluate their efficacy, safety, and stability. Oral (formulation D) and nasal (formulation E) products were developed using specific concentrations of DLM (0.

Effects of organic salts of virucidal and antiviral compounds from Nelumbo nucifera and Kaempferia parviflora against SARS-CoV-2.

The present work investigates virucidal and antiviral compounds in the extracts of seed embryos of a lotus, Nelumbo nucifera, and a Thai ginseng, Kaempferia parviflora. Separation of the extracts led to the identification of antiviral compounds against SARS-CoV-2. Neferine (1) and nuciferine (3) from N.

Virucidal activity of tiliacorinine, dioscorine, racemosol, and terrein against influenza A virus (H1N1), coronavirus 229E, SARS-CoV-2, and enterovirus 71.

Emerging infectious diseases such as COVID-19 and Disease X, which was detected in the Democratic Republic of the Congo in early December 2024, underscore the importance of developing new virucidal, antiviral, and antimicrobial compounds. The virucidal activity of natural products, including tiliacorinine (1), dioscorine (2), racemosol (3), and terrein (4), against influenza A virus (H1N1), human coronavirus 229E (HCoV-229E), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and enterovirus 71 (EV71) were evaluated using the American Society for Testing and Materials E1053-20 method. Racemosol (3) from Bauhinia malabarica had the most potent virucidal activity against the H1N1, HCoV-229E, and SARS-CoV-2 viruses, followed by terrein (4), a metabolite of the fungus Aspergillus terreus.

Regulation of adipocyte differentiation and lipid metabolism by novel synthetic chromenes exploring anti-obesity and broader therapeutic potential.

Obesity poses a significant global health challenge, necessitating the search for novel therapeutic agents to address this epidemic. Chromenes, known for their diverse bioactivities, hold promise as potential anti-obesity compounds, yet research in this area remains limited. This pioneering study represents the first exploration of synthetic chromenes as potential anti-obesity agents, unveiling the underlying molecular pathways governing adipogenesis and lipolysis.

Lanostane Triterpenes, Flavanones and Acetogenins from the Roots of and Their Cytotoxic Activity.

Our phytochemical investigation of the roots of led to the isolation of two new lanostane triterpenes, 3-acetylpolycarpol () and 15-acetylpolycarpol (), as well as 15 known compounds (-). The structures of the isolated compounds were elucidated by an analysis of spectroscopic data. Compounds - were tested against nonsmall cell lung cancer cells (A549) and human cervical carcinoma cells (HeLa) using an MTT assay.

Synthesis, , evaluation of furanyl- and thiophenyl-3-phenyl-1-indole-2-carbohydrazide derivatives as tubulin inhibitors and anticancer agents.

Twenty-one new indole derivatives comprising of seven furanyl-3-phenyl-1-indole-carbohydrazide derivatives and fourteen thiophenyl-3-phenyl-1-indole-carbohydrazide derivatives were synthesised and biologically evaluated for their microtubule-destabilising effects, and antiproliferative activities against the National Cancer Institute 60 (NCI60) human cancer cell line panel. Among the derivatives, 6i showed the best cytotoxic activity exhibiting selectivity for COLO 205 colon cancer (LC = 71 nM), SK-MEL-5 melanoma cells (LC = 75 nM), and MDA-MB-435 (LC = 259 nM). Derivative 6j showed the strongest microtubule-destabilising effect.

Ligand-Based Virtual Screening for Discovery of Indole Derivatives as Potent DNA Gyrase ATPase Inhibitors Active against and Hit Validation by Biological Assays.

is the single most important global infectious disease killer and a World Health Organization critical priority pathogen for development of new antimicrobials. DNA gyrase is a validated target for anti-TB agents, but those in current use target DNA breakage-reunion, rather than the ATPase activity of the GyrB subunit. Here, virtual screening, subsequently validated by whole-cell and enzyme inhibition assays, was applied to identify candidate compounds that inhibit GyrB ATPase activity from the Specs compound library.

Enantioselective Reductive Cyclization of Alkynyl-Tethered Cyclohexadienones Catalyzed by Rhodium Complexes.

Although various types of asymmetric cyclization reactions of 1,6-enynes have been established, simple asymmetric reductive cyclization remains underdeveloped. In this study, the enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones (1,6-enynes) has been developed via a chiral pincer rhodium catalyst, affording -hydrobenzofurans and -hydroindoles with high enantioselectivities (90-99% ee). Furthermore, several synthetic applications and preliminary inhibitory activity studies against SARS-CoV-2 3CL are presented.

Albiflorenes A-L, polyoxygenated cyclohex(a/e)ne diterpene esters from Kaempferia albiflora.

Twelve polyoxygenated cyclohex(a/e)ne diterpene esters, named albiflorenes A-L (1-12), were isolated from the whole plants of Kaempferia albiflora, known as "Prao Mang Mum." Their structures and relative stereochemistry were determined by extensive spectroscopic analysis. Furthermore, the comparison of experimental electronic circular dichroism (ECD) curves with the curves predicted by TDDFT was used to determine the absolute configurations.

Discovery of procyanidin condensed tannins of (-)-epicatechin from Kratom, Mitragyna speciosa, as virucidal agents against SARS-CoV-2.

Kratom, Mitragyna speciosa, is one of the most popular herbs in the West and Southeast Asia. A number of previous works have focused on bioactive alkaloids in this plant; however, non-alkaloids have never been investigated for their biological activities. Antiviral and virucidal assays of a methanol leaf extract of Kratom, M.

Two Cytochrome P450 Enzymes Form the Tricyclic Nested Skeleton of Meroterpenoids by Sequential Oxidative Reactions.

Meroterpenoid clavilactones feature a unique benzo-fused ten-membered carbocyclic ring unit with an α,β-epoxy-γ-lactone moiety, forming an intriguing 10/5/3 tricyclic nested skeleton. These compounds are good inhibitors of the tyrosine kinase, attracting a lot of chemical synthesis studies. However, the natural enzymes involved in the formation of the 10/5/3 tricyclic nested skeleton remain unexplored.

Altenusin, a fungal metabolite, alleviates TGF-β1-induced EMT in renal proximal tubular cells and renal fibrosis in unilateral ureteral obstruction.

Renal fibrosis is a pathological feature of chronic kidney disease (CKD), progressing toward end-stage kidney disease (ESKD). The aim of this study is to investigate the therapeutic potential of altenusin, a farnesoid X receptor (FXR) agonist derived from fungi, on renal fibrosis. The effect of altenusin was determined (i) using the transforming growth factor β1 (TGF-β1)-induced epithelial to mesenchymal transition (EMT) of human renal proximal tubular cells and (ii) using mouse unilateral ureteral obstruction (UUO).

Anti-Xanthine Oxidase 5'-Hydroxyhericenes A-D from the Edible Mushroom and Structure Revision of 3-[2,3-Dihydroxy-4-(hydroxymethyl)tetrahydrofuran-1-yl]-pyridine-4,5-diol.

is an edible mushroom with diverse pharmaceutical applications. Although this mushroom is an attractive source of natural products for cancer treatment, little is known about the bioactive compounds from this mushroom, which may possess antibreast cancer activity. Here, we report the isolation and structure elucidation of new compounds, 5'-hydroxyhericenes A-D () as an inseparable mixture, together with known compounds () from the fruiting body of .

UHPLC-QQQ-MS and RP-HPLC Detection of Bioactive Alizarin and Scopoletin Metabolites from Root Extracts and Their Antitubercular, Antibacterial, and Antioxidant Activities.

is a medicinal plant that has been traditionally used in various therapeutic applications. All parts of including fruits, leaves, stems, roots, and flowers contain various biologically active phytochemicals. This study aimed to evaluate the antitubercular, antibacterial, and antioxidant activities of root extracts and spectroscopically analyze the bioactive metabolites.

The amide derivative of anticopalic acid induces non-apoptotic cell death in triple-negative breast cancer cells by inhibiting FAK activation.

Anticopalic acid (ACP), a labdane type diterpenoid obtained from Kaempferia elegans rhizomes, together with 21 semi-synthetic derivatives, were evaluated for their cancer cytotoxic activity. Most derivatives displayed higher cytotoxic activity than the parent compound ACP in a panel of nine cancer cell lines. Among the tested compounds, the amide 4p showed the highest cytotoxic activity toward leukemia cell lines, HL-60 and MOLT-3, with IC values of 6.

Protein Modification via Nitrile Oxide-Dehydroalanine Cycloaddition: Formation of Isoxazoline Ring on the Protein Backbone.

Here we describe a novel catalyst-free 1,3-dipolar cycloaddition bioconjugation approach for chemical modification of proteins. The dehydroalanine (Dha)-containing protein reacts with nitrile oxides generated in situ through 1,3-dipolar cycloaddition in fully aqueous-buffered systems. This leads to the formation of a new isoxazoline ring at a pre-defined site (Dha) of the protein.

Bioisosteric Design Identifies Inhibitors of DNA Gyrase ATPase Activity.

Mutations in DNA gyrase confer resistance to fluoroquinolones, second-line antibiotics for infections. Identification of new agents that inhibit DNA gyrase ATPase activity is one strategy to overcome this. Here, bioisosteric designs using known inhibitors as templates were employed to define novel inhibitors of DNA gyrase ATPase activity.

Fabrication, Optimization, and Characterization of Antibacterial Electrospun Shellac Fibers Loaded with Extract.

This study aimed to develop a (KP) extract based on electrospun shellac fibers capable of transporting methoxyflavones. This study used a Box-Behnken design to determine the optimal production parameters that influence the fiber diameter and bead-to-fiber ratio responses. The optimization step produced fibers with a small diameter (574 nm) and a lower bead-to-fiber ratio (0.

Traveling Wave Ion Mobility-Derived Collision Cross Section Database for Plant Specialized Metabolites: An Application to Pierre.

The combination of ion mobility mass spectrometry (IM-MS) and chromatography is a valuable tool for identifying compounds in natural products. In this study, using an ultra-performance liquid chromatography system coupled to a high-resolution quadrupole/traveling wave ion mobility spectrometry/time-of-flight MS (UPLC-TWIMS-QTOF), we have established and validated a comprehensive CCS and MS database for 112 plant specialized metabolites. The database included 15 compounds that were isolated and purified in-house and are not commercially available.

Virtual Screening Identifies Novel and Potent Inhibitors of PknB with Antibacterial Activity.

protein kinase B (PknB) is essential to mycobacterial growth and has received considerable attention as an attractive target for novel anti-tuberculosis drug development. Here, virtual screening, validated by biological assays, was applied to select candidate inhibitors of PknB from the Specs compound library (www.specs.