Mechanisms Underlying the Antidiabetic Activities of Polyphenolic Compounds: A Review

Polyphenolic compounds are thought to show considerable promise for the treatment of various metabolic disorders, including type 2 diabetes mellitus (T2DM). This review addresses evidence from in vitro, in vivo, and clinical studies for the antidiabetic effects of certain polyphenolic compounds. We focus on the role of cytotoxic human amylin (hA) aggregates in the pathogenesis of T2DM, and how polyphenols can ameliorate this process by suppressing or modifying their formation. Small, soluble amylin oligomers elicit cytotoxicity in pancreatic islet β-cells and may thus cause β-cell disruption in T2DM. Amylin oligomers may also contribute to oxidative stress and inflammation that lead to the triggering of β-cell apoptosis. Polyphenols may exert antidiabetic effects via their ability to inhibit hA aggregation, and to modulate oxidative stress, inflammation, and other pathways that are β-cell-protective or insulin-sensitizing. There is evidence that their ability to inhibit and destabilize self-assembly by hA requires aromatic molecular structures that bind to misfolding monomers or oligomers, coupled with adjacent hydroxyl groups present on single phenyl rings. Thus, these multifunctional compounds have the potential to be effective against the pleiotropic mechanisms of T2DM. However, substantial further research will be required before it can be determined whether a polyphenol-based molecular entity can be used as a therapeutic for type 2 diabetes.

Estimation of Rate Constants for Reactions of Organic Compounds under Atmospheric Conditions

Structure–activity (SAR) methods are presented for estimating rate constants at 298 K and approximate temperature dependences for the reactions of organic compounds with OH, NO3, and Cl radicals and O3, and O(3P) in the lower atmosphere. These are needed for detailed mechanisms for the atmospheric reactions of organic compounds. Base rate constants are assigned for the various types of H-abstraction and addition reactions, with correction factors for substituents around the reaction site and in some cases for rings and molecule structure or size. Rate constant estimates are made for hydrocarbons and a wide variety of oxygenates, organic nitrates, amines, and monosubstituted halogen compounds. Rate constants for most hydrocarbons and monofunctional compounds can be estimated to within ±30%, though predictions are not as good for multifunctional compounds, and predictions for ~15% of the rate constants are off by more than a factor of 2. Estimates are more uncertain in the case of NO3 and O3 reactions. The results serve to demonstrate the capabilities and limitations of empirical methods for predicting rate constants for the full variety of organic compounds that may be of interest. Areas where future work is needed are discussed.

New Organic Materials Based on Multitask 2H-benzo[d]1,2,3-triazole Moiety

Multifunctionality is a desirable aspect in materials science. Indeed, the development of multifunctional compounds is crucial for sustainable chemistry by saving resources and time. In this sense, 2H-benzo[d]1,2,3-triazole (BTz) is an excellent candidate with promising characteristics, including its ability to self-assemble; its acceptor character, which enables the synthesis of donor-acceptor structures; and its facile modulation using standard chemical methods. Thus, due to its interesting properties, it is possible to produce different derivatives with applications in different fields, as summarized in this article, with the correct substitution at the BTz cores. Optoelectronic or biomedical applications, amongst others, are highlighted.

Design of Multifaceted Antioxidants: Shifting towards Anti-Inflammatory and Antihyperlipidemic Activity

Oxidative stress and inflammation are two conditions that coexist in many multifactorial diseases such as atherosclerosis and neurodegeneration. Thus, the design of multifunctional compounds that can concurrently tackle two or more therapeutic targets is an appealing approach. In this study, the basic NSAID structure was fused with the antioxidant moieties 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHB), its reduced alcohol 3,5-di-tert-butyl- 4-hydroxybenzyl alcohol (BHBA), or 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), a hydrophilic analogue of α-tocopherol. Machine learning algorithms were utilized to validate the potential dual effect (anti-inflammatory and antioxidant) of the designed analogues. Derivatives 1–17 were synthesized by known esterification methods, with good to excellent yields, and were pharmacologically evaluated both in vitro and in vivo for their antioxidant and anti-inflammatory activity, whereas selected compounds were also tested in an in vivo hyperlipidemia protocol. Furthermore, the activity/binding affinity of the new compounds for lipoxygenase-3 (LOX-3) was studied not only in vitro but also via molecular docking simulations. Experimental results demonstrated that the antioxidant and anti-inflammatory activities of the new fused molecules were increased compared to the parent molecules, while molecular docking simulations validated the improved activity and revealed the binding mode of the most potent inhibitors. The purpose of their design was justified by providing a potentially safer and more efficient therapeutic approach for multifactorial diseases.

Ultrasound-Assisted Extraction of Lavender (Lavandula angustifolia Miller, Cultivar Rosa) Solid By-Products Remaining after the Distillation of the Essential Oil

FINNOVER is an EU Interreg-Alcotra project that aims to bring new perspectives to floriculture enterprises by recovering useful bioproducts from the waste produced during processing of several aromatic species. In this study, a new operation strategy to recover lavender (Lavandula angustifolia Mill.) solid by-products remaining after the extraction of the essential oil was developed. Pulsed ultrasound-assisted extraction was employed as a sustainable and eco-compatible technology to extract, in a very short time (10 min), this agricultural waste using a food-grade solvent (a mixture of ethanol/water). All the extracts obtained from both flower and leaf waste and flower-only residues, exhibit a promising total phenolic content (38–40 mg gallic acid/g of dry waste), radical scavenging activity (107–110 mg Trolox/g of dry waste) and total flavonoid content (0.11–0.13 mg quercetin/g of dry waste). Moreover, the chromatographic analysis of these extracts has shown that this overlooked agriculture waste can represent a valuable source of multifunctional compounds. Particularly, they exhibit a content of polyphenols and flavonoids up to 200 times higher than the corresponding leachate, and they are a valuable source of gentisic acid (1.4–13 mg/g dry waste) representing a new low-cost ingredient usable in different fields (i.e., cosmetic).

Atmospheric evolution of emissions from a boreal forest fire: the formation of highly functionalized oxygen-, nitrogen-, and sulfur-containing organic compounds

Forest fires are major contributors of reactive gas- and particle-phase organic compounds to the atmosphere. We used offline high-resolution tandem mass spectrometry to perform a molecular-level speciation of gas- and particle-phase compounds sampled via aircraft from an evolving boreal forest fire smoke plume in Saskatchewan, Canada. We observed diverse multifunctional compounds containing oxygen, nitrogen, and sulfur (CHONS), whose structures, formation, and impacts are understudied. The dilution-corrected absolute ion abundance of particle-phase CHONS compounds increased with plume age by a factor of 6.4 over the first 4 h of downwind transport, and their relative contribution to the observed functionalized organic aerosol (OA) mixture increased from 19 % to 40 %. The dilution-corrected absolute ion abundance of particle-phase compounds with sulfide functional groups increased by a factor of 13 with plume age, and their relative contribution to observed OA increased from 4 % to 40 %. Sulfides were present in up to 75 % of CHONS compounds and the increases in sulfides were accompanied by increases in ring-bound nitrogen; both increased together with CHONS prevalence. A complex mixture of intermediate- and semi-volatile gas-phase organic sulfur species was observed in emissions from the fire and depleted downwind, representing potential precursors to particle-phase CHONS compounds. These results demonstrate CHONS formation from nitrogen- and oxygen-containing biomass burning emissions in the presence of reduced sulfur species. In addition, they highlight chemical pathways that may also be relevant in situations with elevated emissions of nitrogen- and sulfur-containing organic compounds from residential biomass burning and fossil fuel use (e.g., coal), respectively.

Multifunctional compounds for the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common form of dementia, and the prevalence of this currently untreatable disease is expected to rise in step with increased global life expectancy. AD is a multifaceted disorder commonly characterized by extracellular amyloid–beta (Aβ) aggregates, oxidative stress, metal ion dysregulation, and intracellular neurofibrillary tangles. This review will focus on medicinal inorganic chemistry strategies to target AD, with a focus on the Aβ peptide and its relation to metal ion dysregulation and oxidative stress. Multifunctional compounds designed to target multiple disease processes have emerged as promising therapeutic options, and recent reports detailing multifunctional metal-binding compounds, as well as discrete metal complexes, will be discussed.

Enantioselective Decarboxylative Mannich Reaction of β-Keto acids with C-Alkynyl N-Boc N,O-Acetals: Access to Chiral β-Keto Propargylamines

The chiral keto-substituted propargylamines are an essential class of multifunctional compounds in the field of organic and pharmaceutical synthesis and have attracted considerable attention, but the related synthetic approaches remain...