Cinnamic Acid and its derivatives inhibit fructose-mediated protein glycation

Cinnamic acid and its derivatives have shown a variety of pharmacologic properties. However, little is known about the antiglycation properties of cinnamic acid and its derivatives. The present study sought to characterize the protein glycation inhibitory activity of cinnamic acid and its derivatives in a bovine serum albumin (BSA)/fructose system. The results demonstrated that cinnamic acid and its derivatives significantly inhibited the formation of advanced glycation end products (AGEs) by approximately 11.96–63.36% at a concentration of 1 mM. The strongest inhibitory activity against the formation of AGEs was shown by cinnamic acid. Furthermore, cinnamic acid and its derivatives reduced the level of fructosamine, the formation of N^ɛ-(carboxymethyl) lysine (CML), and the level of amyloid cross β-structure. Cinnamic acid and its derivatives also prevented oxidative protein damages, including effects on protein carbonyl formation and thiol oxidation of BSA. Our findings may lead to the possibility of using cinnamic acid and its derivatives for preventing AGE-mediated diabetic complications.     

Kinetics of lipid oxidation in the presence of cinnamic acid derivatives

The effects of seven (prenyl‐ and methoxy‐) derivatives of cinnamic acid (0.1 mM) on the kinetics of lipid (sunflower oil triacylglycerols, TGSO) bulk phase oxidation at 80 °C have been compared. Synthesis of prenyl cinnamic acid derivatives: 3‐prenyl‐4‐hydroxy‐cinnamic acid (PHC), 3,5‐diprenyl‐4‐hydroxy‐cinnamic acid (DPHC), 2,2‐di‐methyl‐6‐carboxy‐ethenyl‐2H‐benzopyran (DMCB), 2,2‐dimethyl‐6‐carboxy‐ethenyl‐8‐prenyl‐2H‐benzopyran (DCEPB) present in Brazilian propolis has been performed. The monoprenyl derivative (PHC) has been found to exert a higher antioxidant activity as compared to the diprenyl derivative (DPHC). However, cinnamic acid derivatives DMCB and DCEPB have caused no change in the kinetics of TGSO oxidation. The results obtained have been compared with those on related compounds containing a cinnamic acid moiety as a structural feature, such as 4‐hydroxy‐cinnamic (p‐coumaric), 3‐methoxy‐4‐hydroxy‐cinnamic (ferulic) and 3,5‐dimethoxy‐4‐hydroxy‐cinnamic (sinapic) acids, as well as with data on butylated hydroxytoluene (BHT) and α‐tocopherol (αToc). PHC has shown a stronger antioxidant efficiency than BHT, p‐coumaric and ferulic acid, but a weaker antioxidant efficiency than α‐Toc and sinapic acid. The observed antioxidant effect of DPHC was stronger than that of p‐coumaric and ferulic acids and weaker than that of α‐Toc, BHT and sinapic acid.     

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

Carbon monoxide (CO) is a bioactive signalling molecule that is produced endogenously via the breakdown of heme. Beneficial health effects associated with the delivery of CO gas have spurred the development of CO‐releasing molecules (CORMs) that can be used to provide specific amounts of the gas. In addition to their potential use as therapeutics, CORMs are needed to provide insight into the biological targets of CO. In this regard, light‐activated CO‐releasing molecules (photoCORMs), are valuable for examining the effects of localized CO release. Herein we examine luminescent CORMs and photoCORMs that have been reported for tracking CO delivery in cells. A variety of motifs are available that exhibit differing luminescence properties and cover a wide range of wavelengths. Trackable CO donors have been successfully applied to targeting CO delivery to mitochondria, thus demonstrating the feasibility of using such molecules in detailed investigations of the biological roles of CO.     

含1,2,3-三氮唑肉桂酸衍生物的合成

1,2,3-三氮唑环作为药效基团呈现出多种生物活性,以4-硝基苯甲醛为原料,合成了叠氮基肉桂酸,并以此为原料,CuI为催化剂,与端基炔烃进行1,3-偶极环加成反应,合成含1,2,3-三氮唑功能基的肉桂酸衍生物。     

Recent advances in small molecule fluorescent probes for simultaneous imaging of two bioactive molecules in live cells and in vivo

The interrelationships and synergistic regulations of bioactive molecules play pivotal roles in physiological and pathological processes involved in the initiation and development of some diseases,such as cancer and neurodegenerative and cardiovascular diseases.Therefore,the simultaneous,accurate and timely detection of two bioactive molecules is crucial to explore their roles and pathological mechanisms in related diseases.Fluorescence imaging associated with small molecular probes has been widely used in the imaging of bioactive molecules in living cells and in vivo due to its excellent performances,including high sensitivity and selectivity,noninvasive properties,real-time and high spatial temporal resolution.Single organic molecule fluorescent probes have been successively developed to simultaneously monitor two biomolecules to uncover their synergistic relationships in living systems.Hence,in this review,we focus on summarizing the design strategies,classifications,and bioimaging applications of dual-response fluorescent probes over the past decade.Furthermore,future research directions in this field are proposed.     

Phytochemical Composition and Biological Activities of Scorzonera Species

The genus Scorzonera comprises nearly 200 species, naturally occurring in Europe, Asia, and northern parts of Africa. Plants belonging to the Scorzonera genus have been a significant part of folk medicine in Asia, especially China, Mongolia, and Turkey for centuries. Therefore, they have become the subject of research regarding their phytochemical composition and biological activity. The aim of this review is to present and assess the phytochemical composition, and bioactive potential of species within the genus Scorzonera. Studies have shown the presence of many bioactive compounds like triterpenoids, sesquiterpenoids, flavonoids, or caffeic acid and quinic acid derivatives in extracts obtained from aerial and subaerial parts of the plants. The antioxidant and cytotoxic properties have been evaluated, together with the mechanism of anti-inflammatory, analgesic, and hepatoprotective activity. Scorzonera species have also been investigated for their activity against several bacteria and fungi strains. Despite mild cytotoxicity against cancer cell lines in vitro, the bioactive properties in wound healing therapy and the treatment of microbial infections might, in perspective, be the starting point for the research on Scorzonera species as active agents in medical products designed for miscellaneous skin conditions.     

Selected Monocyclic Monoterpenes and Their Derivatives as Effective Anticancer Therapeutic Agents

Terpenes—a diverse group of secondary metabolites—constitute the largest class of natural products abundant in almost every plant species. The properties of concrete terpenes and essential oils have been intensively studied due to their widespread use in the pharmaceutical, food and cosmetics industries. Despite the popularity of these aromatic compounds, their derivatives, terpenoids, are still not comprehensively characterized despite exhibiting potent bioactive properties. This review aims to assess the anticancer properties of selected monoterpenes including carvone, carvacrol, perillyl alcohol, perillaldehyde, limonene, menthol and their derivatives while also evaluating potential applications as novel anticancer treatments. Special attention is paid to functional groups that improve the bioactivity of monoterpene molecules. This review also covers the therapeutic potential of deep eutectic solvents that contain monoterpene substances. Taken together, the literature supports the use of monoterpene derivatives in the development of new alternatives for disease treatment and prevention.     

Bone Healing Materials in the Treatment of Recalcitrant Nonunions and Bone Defects

The usual treatment for bone defects and recalcitrant nonunions is an autogenous bone graft. However, due to the limitations in obtaining autogenous bone grafts and the morbidity associated with their procurement, various bone healing materials have been developed in recent years. The three main treatment strategies for bone defects and recalcitrant nonunions are synthetic bone graft substitutes (BGS), BGS combined with bioactive molecules, and BGS and stem cells (cell-based constructs). Regarding BGS, numerous biomaterials have been developed to prepare bone tissue engineering scaffolds, including biometals (titanium, iron, magnesium, zinc), bioceramics (hydroxyapatite (HA)), tricalcium phosphate (TCP), biopolymers (collagen, polylactic acid (PLA), polycaprolactone (PCL)), and biocomposites (HA/MONs@miR-34a composite coating, Bioglass (BG)-based ABVF-BG (antibiotic-releasing bone void filling) putty). Bone tissue engineering scaffolds are temporary implants that promote tissue ingrowth and new bone regeneration. They have been developed to improve bone healing through appropriate designs in terms of geometric, mechanical, and biological performance. Concerning BGS combined with bioactive molecules, one of the most potent osteoinductive growth factors is bone morphogenetic proteins (BMPs). In recent years, several natural (collagen, fibrin, chitosan, hyaluronic acid, gelatin, and alginate) and synthetic polymers (polylactic acid, polyglycolic acid, polylactic-coglycolide, poly(e-caprolactone) (PCL), poly-p-dioxanone, and copolymers consisting of glycolide/trimethylene carbonate) have been investigated as potential support materials for bone tissue engineering. Regarding BGS and stem cells (cell-based constructs), the main strategies are bone marrow stromal cells, adipose-derived mesenchymal cells, periosteum-derived stem cells, and 3D bioprinting of hydrogels and cells or bioactive molecules. Currently, significant research is being performed on the biological treatment of recalcitrant nonunions and bone defects, although its use is still far from being generalized. Further research is needed to investigate the efficacy of biological treatments to solve recalcitrant nonunions and bone defects.     

Oncostatic-Cytoprotective Effect of Melatonin and Other Bioactive Molecules: A Common Target in Mitochondrial Respiration

For several years, oncostatic and antiproliferative properties, as well as thoses of cell death induction through 5-methoxy-N-acetiltryptamine or melatonin treatment, have been known. Paradoxically, its remarkable scavenger, cytoprotective and anti-apoptotic characteristics in neurodegeneration models, such as Alzheimer’s disease and Parkinson’s disease are known too. Analogous results have been confirmed by a large literature to be associated to the use of many other bioactive molecules such as resveratrol, tocopherol derivatives or vitamin E and others. It is interesting to note that the two opposite situations, namely the neoplastic pathology and the neurodegeneration, are characterized by deep alterations of the metabolome, of mitochondrial function and of oxygen consumption, so that the oncostatic and cytoprotective action can find a potential rationalization because of the different metabolic and mitochondrial situations, and in the effect that these molecules exercise on the mitochondrial function. In this review we discuss historical and general aspects of melatonin, relations between cancers and the metabolome and between neurodegeneration and the metabolome, and the possible effects of melatonin and of other bioactive molecules on metabolic and mitochondrial dynamics. Finally, we suggest a common general mechanism as responsible for the oncostatic/cytoprotective effect of melatonin and of other molecules examined.     

Glycosylated Cell-Penetrating Peptides (GCPPs)

The cell membrane regulates the exchange of molecules and information with the external environment. However, this control barrier hinders the delivery of exogenous bioactive molecules that can be applied to correct cellular malfunctions. Therefore, the traffic of macromolecules across the cell membrane represents a great challenge for the development of the next generation of therapies and diagnostic methods. Cell-penetrating peptides are short peptide sequences capable of delivering a broad range of biomacromolecules across the cellular membrane. However, penetrating peptides still suffer from limitations, mainly related to their lack of specificity and potential toxicity. Glycosylation has emerged as a potential promising strategy for the biological improvement of synthetic materials. In this work we have developed a new convergent strategy for the synthesis of penetrating peptides functionalized with glycan residues by an oxime bond connection. The uptake efficiency and intracellular distribution of these glycopeptides have been systematically characterized by means of flow cytometry and confocal microscopy and in zebrafish animal models. The incorporation of these glycan residues into the peptide structure influenced the internalization efficiency and cellular toxicity of the resulting glycopeptide hybrids in the different cell lines tested. The results reported herein highlight the potential of the glycosylation of penetrating peptides to modulate their activity.     

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects. Thus, single-target therapy has drawbacks in the effective control of tubulin polymerization. Molecular hybridization, based on the amalgamation of two or more pharmacophores of bioactive conjugates to engender a single molecular structure with enhanced pharmacokinetics and biological activity, compared to their parent molecules, has recently become a promising approach in drug development. The practical application of combined active scaffolds targeting tubulin polymerization inhibitors has been corroborated in the past few years. Meanwhile, different designs and syntheses of novel anti-tubulin hybrids have been broadly studied, illustrated, and detailed in the literature. This review describes various molecular hybrids with their reported structural–activity relationships (SARs) where it is possible in an effort to generate efficacious tubulin polymerization inhibitors. The aim is to create a platform on which new active scaffolds can be modeled for improved tubulin polymerization inhibitory potency and hence, the development of new therapeutic agents against cancer.     

Curcumin and Its Derivatives as Theranostic Agents in Alzheimer’s Disease: The Implication of Nanotechnology

Curcumin is a polyphenolic natural compound with diverse and attractive biological properties, which may prevent or ameliorate pathological processes underlying age-related cognitive decline, Alzheimer’s disease (AD), dementia, or mode disorders. AD is a chronic neurodegenerative disorder that is known as one of the rapidly growing diseases, especially in the elderly population. Moreover, being the eminent cause of dementia, posing problems for families, societies as well a severe burden on the economy. There are no effective drugs to cure AD. Although curcumin and its derivatives have shown properties that can be considered useful in inhibiting the hallmarks of AD, however, they have low bioavailability. Furthermore, to combat diagnostic and therapeutic limitations, various nanoformulations have also been recognized as theranostic agents that can also enhance the pharmacokinetic properties of curcumin and other bioactive compounds. Nanocarriers have shown beneficial properties to deliver curcumin and other nutritional compounds against the blood-brain barrier to efficiently distribute them in the brain. This review spotlights the role and effectiveness of curcumin and its derivatives in AD. Besides, the gut metabolism of curcumin and the effects of nanoparticles and their possible activity as diagnostic and therapeutic agents in AD also discussed.     

Deep Eutectic Solvent as Green Solvent in Extraction of Biological Macromolecules: A Review

Greater awareness of environmental sustainability has driven many industries to transition from using synthetic organic solvents to greener solvents in their manufacturing. Deep eutectic solvents (DESs) have emerged as a highly promising category of green solvents with well-demonstrated and wide-ranging applications, including their use as a solvent in extraction of small-molecule bioactive compounds for food and pharmaceutical applications. The use of DES as an extraction solvent of biological macromolecules, on the other hand, has not been as extensively studied. Thereby, the feasibility of employing DES for biomacromolecule extraction has not been well elucidated. To bridge this gap, this review provides an overview of DES with an emphasis on its unique physicochemical properties that make it an attractive green solvent (e.g., non-toxicity, biodegradability, ease of preparation, renewable, tailorable properties). Recent advances in DES extraction of three classes of biomacromolecules—i.e., proteins, carbohydrates, and lipids—were discussed and future research needs were identified. The importance of DES’s properties—particularly its viscosity, polarity, molar ratio of DES components, and water addition—on the DES extraction’s performance were discussed. Not unlike the findings from DES extraction of bioactive small molecules, DES extraction of biomacromolecules was concluded to be generally superior to extraction using synthetic organic solvents.     

Polymers used to influence cell fate in 3D geometry: New trends

The extracellular matrix (ECM) is a hydrogel-like structure comprised of several different biopolymers, encompassing a wide range of biological, chemical, and mechanical properties. The composition, organization, and assembly of the ECM play a critical role in cell function. Cellular behavior is guided by interactions that occur between cells and their local microenvironment, and this interrelationship plays a significant role in determining physiological functions. Bioengineering approaches have been developed to mimic native tissue microenvironments by fabricating novel bioactive hydrogel scaffolds. This review explores material designs and fabrication approaches that are guiding the design of hydrogels as tissue engineered scaffolds. As the fundamental biology of the cellular microenvironment is often the inspiration for material design, the review focuses on modifications to control bioactive cues such as adhesion molecules and growth factors, and summarizes the current applications of biomimetic scaffolds that have been used in vitro as well as in vivo.     

噻唑/·唑类活性天然产物及活性小分子化合物研究进展

介绍了天然界中存在很多含有噻唑/(口恶)唑结构单元的活性分子,其生物合成途径或仿生合成方法通常分别以多肽氨基酸残基的羧酸基团或羧酸衍生物为底物,与半胱氨酸/丝氨酸等天然氨基酸或经过衍生化的非天然氨基酸环合、氧化而成,因此天然产物中的噻唑/(口恶)唑C5位通常以无取代的形式存在。然而,C5位二聚化、烯基化或芳基化的噻唑/(口恶)唑结构单元常见于具有广泛药理活性的人工合成的分子中,构建这类结构单元通常都需预先制备β-取代的非天然氨基酸。并且,关于该类天然产物的结构改造均未涉及噻唑/(口恶)唑C5位上的官能团化修饰,这是由于目前尚缺乏该位点上的官能团化方法而造成的。该现状预示着,开发噻唑/(口恶)唑C5位官能团化新方法,并将其应用于噻唑/(口恶)唑天然产物的结构修饰,具有十分重要的意义和研究价值。     

Imidazole- and imidazolium-containing polymers for biology and material science applications

The imidazole ring is ubiquitous in nature and imidazole functionality plays a critical role in many structures within the human body, notably as histamine and histadine. Imidazoles offer many biophysical interactions including their ability to hydrogen bond with drugs and proteins. In contrast, imidazolium salts have lost their strong hydrogen-bonding ability through alkylation of both nitrogens, but they are able to aggregate electrostatically. Imidazolium salts are used to extract metal ions from aqueous solutions, dissolve carbohydrates, create polyelectrolyte brushes on surfaces, coat metal nanoparticles, provide antimicrobial action, and create oriented liquid crystals. Bioactive applications include imidazolium hydrogels, antiarrhythmics, and anti-metastic agents. This review will describe the synthesis and design of imidazole derivatives and imidazolium-containing polymers as bioactive materials. Imidazole-based polymers readily associate with biological molecules through hydrogen-bonding, and imidazolium analogs offer electrostatic interactions, aggregation, and self-assembly. Design of novel imidazole- and imidazolium-based macromolecules remains as an exciting and emerging field.     

Development of Polyamine-Substituted Triphenylamine Ligands with High Affinity and Selectivity for G-Quadruplex DNA

Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid–base properties of the new derivatives have been studied by means of potentiometric titrations, UV/Vis and fluorescence emission spectroscopy. The interaction with G4s and duplex DNA has been explored by using FRET melting assays, fluorescence spectroscopy and circular dichroism. Compared with previous TPA derivatives with macrocyclic substituents, the new ligands reported herein retain the G4 affinity, but display two orders of magnitude higher selectivity for G4 versus duplex DNA; this is most likely due to the ability of the linear substituents to embrace the G4 structure.     

KYNA Derivatives with Modified Skeleton; Hydroxyquinolines with Potential Neuroprotective Effect

Kynurenic acid (KYNA) is an endogenous neuroprotective agent of increasing importance. Several derivatives have already been synthesized, bearing an abundance of functional groups attached to the main skeleton in different positions. Several of these compounds have already been tested in biological evaluations, with several of them targeting the same receptors and biological effects as KYNA. However, these modified compounds build upon the unmodified KYNA skeleton leaving a possible route for the synthesis of new, potentially neuroprotective derivatives with heteroatom-containing ring systems. The aim of this review is to summarize the syntheses of KYNA derivatives with altered skeletons and to pinpoint an appealing transformation for future medicinal lead molecules.     

Morpholine As a Scaffold in Medicinal Chemistry: An Update on Synthetic Strategies

Morpholine is a frequently used heterocycle in medicinal chemistry and a privileged structural component of bioactive molecules. This is mainly due to its contribution to a plethora of biological activities as well as to an improved pharmacokinetic profile of such bioactive molecules. The synthesis of morpholines is a subject of much study due to their biological and pharmacological importance, with the last such review being published in 2013. Here, an overview of the main approaches toward morpholine synthesis or functionalization is presented, emphasizing on novel work which has not been reviewed so far. This review is an update on synthetic strategies leading to easily accessible libraries of bioactives which are of interest for drug discovery projects.     

Endohedral and exohedral hybrids involving fullerenes and carbon nanotubes

Since fullerenes and carbon nanotubes (CNTs) were discovered, these materials have attracted a great deal of attention in the scientific community due to their unique structures and properties. The properties of both carbon allotropes can be modulated by chemical functionalization, and merging fullerenes and CNTs combines the electronic and optical properties of CNTs with the excellent electron acceptor characteristic of fullerenes; moreover, a synergistic effect of these hybrids can be found, as the properties of both the nanotube and the fullerene are affected by the presence of the other. In these hybrids, the fullerene can be located inside (endohedral) or outside (exohedral) the CNT and both types of hybrid have specific features. CNT-fullerene hybrids have been studied for various applications, including photovoltaics, optical limiting and flame retardancy amongst others. This review outlines the progress in research on CNT-fullerene hybrids, including endohedral and exohedral combinations, their properties, functionalization, applications and outlook.