Redox Status-Selective Imaging of Iron in Vegetative and Pathogenic Fungal Cells Using Fluorescent Dyes Synthesized Via Simple Chemical Reactions.

Iron plays a prominent role in various biological processes and is an essential element in almost all organisms, including plant-pathogenic fungi. As a transition element, iron occurs in two redox states, Fe and Fe, the transition between which generates distinct reactive oxygen species (ROS) such as HO, OH anions, and toxic OH· radicals. Thus, the redox status of Fe determines ROS formation in pathogen attack and plant defense and governs the outcome of pathogenic interactions.

Two New α-Glucosidase Inhibitors from Haplophyllum tuberculatum: Inhibition Kinetics and Mechanistic Insights Through in Vitro and in Silico Approaches.

Diabetes is a multifactorial global health disorder marked by unusually high plasma glucose levels, which can lead to serious consequences including diabetic neuropathy, kidney damage, retinopathy, and cardiovascular disease. One effective therapy approach for reducing hyperglycemia associated with type 2 diabetes is to target α-glucosidase, enzymes that catalyze starch breakdown in the intestine. In the current study, two new (1, 2) and nine known (3-11) compounds were isolated from the rutaceous plant Haplophyllum tuberculatum and characterized by extensive nuclear magnetic resonance spectroscopic techniques and high-resolution electrospray ionization mass spectrometry.

Dihydrofolate reductase inhibitory potential of 1H-indole-based-meldrum linked 1H-1,2,3-triazoles as new anticancer derivatives: In-vitro and in-silico studies.

In this present work, we describe the syntheses of a new series of 32 1H-indole-based-meldrum linked 1H-1,2,3-triazole derivatives (2-13, 15a-15f, 16a-16f, 17a-17f and 19a, 19b, 20a), which constitute a new class of 1H-1,2,3-triazoles. Compounds 15a-15f, 16a-16f, 17a-17f have been prepared by employing "click" reactions between substituted 1H-indole-based meldrum alkynes (11, 12 and 13) and substituted aromatic azides (14a-14f) in the presence of copper iodide (CuI) and Hünig's base. Then, the synthesis of compounds 19, 20 through decomposition of meldrum moiety.

Novel Anti-Tumor Effect of Natural Products from Aloe vera Resin and their In-Vitro/In-Silico Targeting Mechanism of Carbonic Anhydrase-II and IX.

Human carbonic anhydrase (hCA) plays a vital role in the development and progression of tumors in hypoxic conditions. Herein we report the hCA-II and hCA-IX activities of natural products isolated from Aloe vera (L.) Burm.

Triterpenoids from Frankincense and Boswellia: A focus on their pharmacology and C-NMR assignments.

Here we report for the first time the entire C-NMR spectral assignments of 119 (out of 127) triterpenoids from the oleo-gum resins of the medicinally important genus Boswellia, which includes the culturally highly valuable Frankincense species. The complete C-NMR resonances of these triterpenoids isolated between 1998 and 2024 and their biological activities are presented. C-NMR spectroscopy is a highly powerful tool for the characterization of these bioactive natural products.

Elongation of Very Long-Chain Fatty Acids (ELOVL) in Atopic Dermatitis and the Cutaneous Adverse Effect AGEP of Drugs.

Atopic dermatitis (AD) is a common inflammatory skin disease, in particular among infants, and is characterized, among other things, by a modification in fatty acid and ceramide composition of the skin's stratum corneum. Palmitic acid and stearic acid, along with C-ceramide and 2-hydroxy C-ceramide, occur strikingly in AD. They coincide with a simultaneous decrease in very long-chain ceramides and ultra-long-chain ceramides, which form the outermost lipid barrier.

Disrupting protease and deubiquitinase activities of SARS-CoV-2 papain-like protease by natural and synthetic products discovered through multiple computational and biochemical approaches.

The single-stranded RNA genome of SARS-CoV-2 encodes several structural and non-structural proteins, among which the papain-like protease (PLpro) is crucial for viral replication and immune evasion and has emerged as a promising therapeutic target. The current study aims to discover new inhibitors of PLpro that can simultaneously disrupt its protease and deubiquitinase activities. Using multiple computational approaches, six compounds (CP1-CP6) were selected from our in-house compounds database, with higher docking scores (-7.

Synthesis and Enzymatic Evaluation of a Small Library of Substituted Phenylsulfonamido-Alkyl Sulfamates towards Carbonic Anhydrase II.

A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, -, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates -, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds - showed no inhibition of the enzyme, in contrast to sulfamates -.

Diethoxyphosphoryloxy-oleanolic acid is a nanomolar-inhibitor of butyrylcholinesterase.

A series of new betulin, lupeol, erythrodiol, and oleanolic acid phosphoryloxy- and furoyloxy-derivatives has been synthesized and their structure was confirmed by NMR spectroscopy. Synthesized compounds were subjected to Ellman's assays to determine their ability to inhibit the enzymes AChE and BChE. Among them, diethoxyphosphoryloxy-oleanolic acid inhibited BChE with a value of 99%, thereby acting as a mixed-type inhibitor holding very low K values of Ki = 6.

An asiatic acid derived trisulfamate acts as a nanomolar inhibitor of human carbonic anhydrase VA.

This investigation delves into the inhibitory capabilities of a specific set of triterpenoic acids on diverse isoforms of human carbonic anhydrase (hCA). Oleanolic acid (1), maslinic acid (2), betulinic acid (3), platanic acid (4), and asiatic acid (5) were chosen as representative triterpenoids for evaluation. The synthesis involved acetylation of parent triterpenoic acids 1-5, followed by sequential reactions with oxalyl chloride and benzylamine, de-acetylation of the amides, and subsequent treatment with sodium hydride and sulfamoyl chloride, leading to the formation of final compounds 21-25.

Ureidobenzenesulfonamides as Selective Carbonic Anhydrase I, IX, and XII Inhibitors.

Sulfonamides remain an important class of drugs, especially because of their inhibitory effects on carbonic anhydrases. Herein, we have synthesized several sulfonamides and tested them for their inhibitory activity against carbonic anhydrases hCA I, hCA II, hCA IX, and hCA XII, respectively. Thereby, biphenyl- and benzylphenyl-substituted sulfonamides showed high selectivity against hCA IX and hCA XII; these enzymes are common targets in the treatment of hypoxic cancers, and noteworthy inhibitory activity was observed for several compounds toward hCA I that might be of interest for future applications to treat cerebral edema.

Ready-to-use nanopore platform for label-free small molecule quantification: Ethanolamine as first example.

In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS.

Inhibitory properties of quinopimaric acid derivatives towards cholinesterases.

A series of new diterpene quinopimaric acid derivatives modified at the hydroxyl group with different pharmacophore fragments has been synthesised and their (along with previously obtained compounds) inhibitory properties towards cholinesterases were studied. Thereby an indole-3-acetyl derivative and a propargyl substituted compound were shown to be excellent and acetylcholinesterase-selective inhibitors. Both compounds inhibited the enzyme as a mixed type inhibitor, and K values of 0.

Developing an Amide-Spacered Triterpenoid Rhodamine Hybrid of Nano-Molar Cytotoxicity Combined with Excellent Tumor Cell/Non-Tumor Cell Selectivity.

Asiatic acid, a pentacyclic triterpene, was converted into a series of piperazinyl, homopiperazinyl, and 1,5-diazocinyl spacered rhodamine conjugates, differing in the type of spacer and the substitution pattern on the rhodamine moiety of the hybrids. The compounds were tested for cytotoxic activity in SRB assays and compound , holding an EC of 0.8 nM, was the most cytotoxic compound of this series, but compound (containing a ring expanded 1,5-diazocinyl moiety and -propyl substituents on the rhodamine) was the most selective compound exhibiting a selectivity factor of almost 190 while retaining high cytotoxicity (EC = 1.

Substrate-like novel inhibitors of prolyl specific oligo peptidase for neurodegenerative disorders.

Prolyl specific oligopeptidase (POP), is one of the highly expressed enzymes in the brain and is a prime target to treat disorders related to the central nervous system. Here, we describe the structure-based design of the tacrine derivatives, selective, and brain-permeable POP inhibitors. These compounds inactivate POP in-vitro specifically and sustainably at very low concentrations (nano molar).

Meldrum-Based-1-1,2,3-Triazoles as Antidiabetic Agents: Synthesis, α-Glucosidase Inhibition Activity, Molecular Docking Studies, and Approach.

A series of novel alkyl derivatives () and 1-1,2,3-triazole analogues () of Meldrum's acid were synthesized in a highly effective way by using chemistry and screened for in vitro -glucosidase inhibitory activity to examine their antidiabetic potential. H NMR, C-NMR, and high-resolution electrospray ionization mass spectra (HR-ESI-MS) were used to analyze each of the newly synthesized compounds. Interestingly, these compounds demonstrated high to moderate α-glucosidase inhibitory potency having an IC range of 4.

Targeted theranostics: Near-infrared triterpenoic acid-rhodamine conjugates as prerequisites for precise cancer diagnosis and therapy.

Pentacyclic triterpenoic acids have shown excellent potential as starting materials for the synthesis of highly cytotoxic agents with significantly reduced toxicity for non-malignant cells. This study focuses on the development of triterpenoic acid-rhodamine conjugates with fluorescence shifted to the near-infrared (NIR) region for theranostic applications in cancer research. Spectral analysis revealed emission wavelengths around λ = 760 nm, enabling stronger signals and deeper tissue penetration.

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.

The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation.