Synthesis of BODIPY-pyrrolo[3,4-]pyridin-5-ones Ugi-Zhu/cascade reactions and studies of fluorescence response toward viscosity.

A series of seven new -phenyl BODIPY-pyrrolo[3,4-]pyridin-5-one conjugates were synthesized in one experimental step by using a Sc(III)-catalyzed Ugi-Zhu three-component reaction coupled to a cascade sequence ( Diels-Alder/-acylation/aromatization) as post-MCR functionalization process. Further experimental studies were performed behind understanding the fluorescence response toward viscosity. All compounds exhibited a linear response between increasing viscosity (DMSO and glycerol mixtures) and fluorescence intensity.

Evaluating Quinolines: Molecular Dynamics Approach to Assess Their Potential as Acetylcholinesterase Inhibitors for Alzheimer's Disease.

Quinoline represents a promising scaffold for developing potential drugs because of the wide range of biological and pharmacological activities that it exhibits. In the present study, quinoline derivatives obtained from CADMA-Chem docking protocol were investigated in the mean of molecular dynamics simulations as potential inhibitors of acetylcholinesterase enzyme. The examined species can be partitioned between neutral, dq815 (2,3 dihydroxyl-quinoline-4-carbaldehyde), dq829 (2,3 dihydroxyl-quinoline-8-carboxylic acid methane ester), dq1356 (3,4 dihydroxyl-quinoline-6-carbaldehyde), dq1368 (3,4 dihydroxyl-quinoline-8-carboxylic acid methane ester) and dq2357 (5,6 dihydroxyl-quinoline-8-carboxylic acid methane ester), and deprotonated, dq815_dep, dq829_dep, dq1356_dep and dq2357_dep.

On the dual role of (+)-catechin as primary antioxidant and inhibitor of viral proteases.

Natural antioxidants have become the subject of many investigations due to the role that they play in the reduction of oxidative stress. Their main scavenging mechanisms concern the direct inactivation of free radicals and the coordination of metal ions involved in Fenton-like reactions. Recently, increasing attention has been paid to non-covalent inhibition of enzymes involved in different diseases by the antioxidants.

Calmodulin-Targeting Molecules from .

Four new natural chemical entities, including 2-hydroxy-α-truxillic acid (), (3,4)-2,2-dimethyl-3-hydroxy-4-(1-angeloyloxy)-6-acetyl-7-methoxychromane (), -tricosanoyltyramine (), and grandifolamide (), were isolated along with 11 known compounds (, -) from the aerial parts of . The chemical structures were elucidated using chemical derivatization and HR-MS, NMR, and DFT-calculated chemical shifts, combined with DP4+ statistical analysis. It was found that decomposed into its biogenetic precursor, -coumaric acid, upon standing at room temperature for a few weeks.

Quinoline Derivatives: Promising Antioxidants with Neuroprotective Potential.

Quinoline has been proposed as a privileged molecular framework in medicinal chemistry. Although by itself it has very few applications, its derivatives have diverse biological activities. In this work, 8536 quinoline derivatives, strategically designed using the CADMA-Chem protocol, are presented.

Rational Design of Multifunctional Ferulic Acid Derivatives Aimed for Alzheimer's and Parkinson's Diseases.

Ferulic acid has numerous beneficial effects on human health, which are frequently attributed to its antioxidant behavior. In this report, many of them are reviewed, and 185 new ferulic acid derivatives are computationally designed using the CADMA-Chem protocol. Consequently, their chemical space was sampled and evaluated.

CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants.

A computational protocol aimed to design new antioxidants with versatile behavior is presented. It is called Computer-Assisted Design of Multifunctional Antioxidants and is based on chemical properties (CADMA-Chem). The desired multi-functionality consists of in different methods of antioxidant protection combined with neuroprotection, although the protocol can also be used to pursue other health benefits.

Chalcone Derivatives with a High Potential as Multifunctional Antioxidant Neuroprotectors.

A systematic, rational search for chalcone derivatives with multifunctional behavior has been carried out, with the support of a computer-assisted protocol (CADMA-Chem). A total of 568 derivatives were constructed by incorporating functional groups into the chalcone structure. Selection scores were calculated from ADME properties, toxicity, and manufacturability descriptors.

Antioxidants into Nopal (), Important Inhibitors of Free Radicals' Formation.

Nopal () belonging to the Cactacea family has many nutritional benefits attributed to a wide variety of phenolic and flavonoid compounds. Coumaric acid (COA), ferulic acid (FLA), protocatechuic acid (PRA), and gallic acid (GAA) are the phenolic acids (PhAs) present in nopal. In this study, the role of these PhAs in copper-induced oxidative stress was investigated using the density functional theory (DFT).

Potentiating the Benefits of Melatonin through Chemical Functionalization: Possible Impact on Multifactorial Neurodegenerative Disorders.

Although melatonin is an astonishing molecule, it is possible that chemistry will help in the discovery of new compounds derived from it that may exceed our expectations regarding antioxidant protection and perhaps even neuroprotection. This review briefly summarizes the significant amount of data gathered to date regarding the multiple health benefits of melatonin and related compounds. This review also highlights some of the most recent directions in the discovery of multifunctional pharmaceuticals intended to act as one-molecule multiple-target drugs with potential use in multifactorial diseases, including neurodegenerative disorders.

Capsaicin, a Powerful OH-Inactivating Ligand.

Oxidative conditions are frequently enhanced by the presence of redox metal ions. In this study, the role of capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) in copper-induced oxidative stress was investigated using density functional theory simulations. It was found that CAP has the capability to chelate Cu(II), leading to complexes that are harder to reduce than free Cu(II).

Computationally Designed Sesamol Derivatives Proposed as Potent Antioxidants.

Oxidative stress has been recognized to play an important role in several diseases, such as Parkinson's and Alzheimer's disease, which justifies the beneficial effects of antioxidants in ameliorating the deleterious effects of these health disorders. Sesamol, in particular, has been investigated for the treatment of several conditions because of its antioxidant properties. This article reports a rational computational design of new sesamol derivatives.

The Antioxidant Capability of Higenamine: Insights from Theory.

Density functional theory was employed to highlight the antioxidant working mechanism of higenamine in aqueous and lipid-like environments. Different reaction mechanisms were considered for the reaction of higenamine with the OOH radical. The pH values and the molar fraction at physiological pH were determined in aqueous solution.

Detailed Investigation of the Outstanding Peroxyl Radical Scavenging Activity of Two Novel Amino-Pyridinol-Based Compounds.

The ability of two novel amino-pyridinol based compounds (NPyr6 and NPyr7) as peroxyl radical scavengers was investigated . The gathered data indicate that they are exceptionally efficient in that role. However, solvent polarity influences their relative efficiency for that purpose.

The other side of the superoxide radical anion: its ability to chemically repair DNA oxidized sites.

The superoxide radical anion can repair oxidative damage. In particular, it was demonstrated that O2˙- can repair oxidized DNA by electron transfer, restoring the original structure of this important molecule. Acid-base equilibria have been considered, and the influence of the pH on the main reaction mechanism has been explored.

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA.

Oxidative stress mediates chemical damage to DNA yielding a wide variety of products. In this work, the potential capability of melatonin and several of its metabolites to repair directly (chemically) oxidative lesions in DNA was explored. It was found that all the investigated molecules are capable of repairing guanine-centered radical cations by electron transfer at very high rates, that is, diffusion-limited.

The reactions of plant hormones with reactive oxygen species: chemical insights at a molecular level.

The reactions of two plant hormones, namely jasmonic acid (JA) and methyl jasmonate (MJ), with different reactive oxygen species (ROS) were investigated using the density functional theory. Different reaction sites and mechanisms were explored, as well as solvents of different polarity, and pH in aqueous solution. The thermochemical viability and kinetics of the investigated reaction pathways were found to be strongly influenced by the reacting ROS.

Melatonin Mitigates Mitochondrial Meltdown: Interactions with SIRT3.

Melatonin exhibits extraordinary diversity in terms of its functions and distribution. When discovered, it was thought to be uniquely of pineal gland origin. Subsequently, melatonin synthesis was identified in a variety of organs and recently it was shown to be produced in the mitochondria.

Scavenging Ability of Homogentisic Acid and Ergosterol toward Free Radicals Derived from Ethanol Consumption.

Acute, or chronic, ethanol consumption leads to the formation of free radicals in the liver, which is related to hepatic damage. Among these radicals 1-hydroxyethyl, CH(OH)CH, is the most abundant one. Thus, efficient CH(OH)CH scavengers are likely candidates to offer liver protection after ethanol consumption.

Melatonin and its metabolites vs oxidative stress: From individual actions to collective protection.

Oxidative stress (OS) represents a threat to the chemical integrity of biomolecules including lipids, proteins, and DNA. The associated molecular damage frequently results in serious health issues, which justifies our concern about this phenomenon. In addition to enzymatic defense mechanisms, there are compounds (usually referred to as antioxidants) that offer chemical protection against oxidative events.

Comprehensive Investigation of the Antioxidant and Pro-oxidant Effects of Phenolic Compounds: A Double-Edged Sword in the Context of Oxidative Stress?

Oxidative stress (OS) is a health-threatening process that is involved, at least partially, in the development of several diseases. Although antioxidants can be used as a chemical defense against OS, they might also exhibit pro-oxidant effects, depending on environmental conditions. In this work, such a dual behavior was investigated for phenolic compounds (PhCs) within the framework of the density functional theory and based on kinetic data.

Chemical Insights into the Antioxidant Mechanisms of Alkylseleno and Alkyltelluro Phenols: Periodic Relatives Behaving Differently.

The possible antioxidant reaction mechanisms of recently synthesized and tested alkylseleno (telluro) phenols have been explored using density functional theory by considering two solvents physiologically relevant, water and pentylethanoate (PE). In addition, the possible pathway for the antioxidant regeneration with ascorbic acid has been investigated. Results show that selenium and tellurium systems follow different chemical behaviors.

Synthesis, Characterization, and Solid State Dynamic Studies of a Hydrogen Bond-Hindered Steroidal Molecular Rotor with a Flexible Axis.

A novel steroid molecular rotor was obtained in four steps from the naturally occurring spirostane sapogenin diosgenin. The structural and dynamic characterization was carried out by solution NMR, VT X-ray diffraction, solid state C CPMAS, and solid state H NMR experiments. They allowed the identification of a fast dynamic process with a frequency of 14 MHz at room temperature, featuring a barrier to rotation Ea = 7.

Melatonin: A Versatile Protector against Oxidative DNA Damage.

Oxidative damage to DNA has important implications for human health and has been identified as a key factor in the onset and development of numerous diseases. Thus, it is evident that preventing DNA from oxidative damage is crucial for humans and for any living organism. Melatonin is an astonishingly versatile molecule in this context.

Mitochondria: Central Organelles for Melatonin's Antioxidant and Anti-Aging Actions.

Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations.