两个带呋喃悬臂不对称大环双核铜配合物的合成、结构及性质

合成并表征了2个不对称大环双核铜配合物[Cu₂（L¹）Cl₂]·CH₃CN（1）和[Cu₂（L²）Br₂]·CH₃CN·H₂O（2）。配合物与CT-DNA的作用通过紫外-可见光谱,粘度实验,圆二色谱和凝胶电泳实验进行了研究。紫外-可见光谱的结果表明配合物与DNA的结合常数分别为6.2×10⁵和7.2×10⁵,圆二色谱的实验表明配合物能与DNA较好的结合,粘度实验表明配合物与DNA的结合为非典型的插入模式,凝胶电泳实验显示配合物通过氧化机理对DNA有较强的切割活性。     

Development of aqueous oxidative Ugi-type reactions by copper-catalyzed surfactant-promoted C(sp)–H direct functionalization in water

Direct assembly of α-amino amides from N-alkyl amines and isocyanides through oxidative Ugi-type reactions in aqueous conditions, has been achieved in a Cu(I)–TBHP–surfactant catalysis system. Various N-alkyl amines and isocyanides could be tolerated in this reaction and furnish α-amino amides in moderate yields.     

Tandem Synthesis of Tetrasubstituted NH Pyrroles from Simple Nitriles

An efficient tandem route to obtain tetrasubstituted NH pyrroles in a one-pot manner has been developed, staring from simple nitriles, ethyl bromoacetates, and zinc. This reaction involves oxidative dimerization of the zinc bromide complex of β-enaminoesters using cerium ammonium nitrate (CAN) as an oxidant, affording 2,3,4,5-tetrasubstituted pyrroles in yields up to 91%.     

Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.     

Activity Guided Isolation of Phenolic Compositions from Anneslea fragrans Wall. and Their Cytoprotective Effect against Hydrogen Peroxide Induced Oxidative Stress in HepG2 Cells

Anneslea fragrans Wall., commonly known as “Pangpo Tea”, is traditionally used as a folk medicine and healthy tea for the treatment of liver and intestine diseases. The aim of this study was to purify the antioxidative and cytoprotective polyphenols from A. fragrans leaves. After fractionation with polar and nonpolar organic solvents, the fractions of aqueous ethanol extract were evaluated for their total phenolic (TPC) and flavonoid contents (TFC) and antioxidant activities (DPPH, ABTS, and FRAP assays). The n-butanol fraction (BF) showed the highest TPC and TFC with the strongest antioxidant activity. The bio-guided chromatography of BF led to the purification of six flavonoids (1–6) and one benzoquinolethanoid (7). The structures of these compounds were determined by NMR and MS techniques. Compound 6 had the strongest antioxidant capacity, which was followed by 5 and 2. The protective effect of the isolated compounds on hydrogen peroxide (H₂O₂)-induced oxidative stress in HepG2 cells revealed that the compounds 5 and 6 exhibited better protective effects by inhibiting ROS productions, having no significant difference with vitamin C (p > 0.05), whereas 6 showed the best anti-apoptosis activity. The results suggest that A. fragrans could serve as a valuable antioxidant phytochemical source for developing functional food and health nutraceutical products.     

Quantification of Intracellular Thiols by HPLC-Fluorescence Detection

Biothiols, such as cysteine and glutathione, play important roles in various intracellular reactions represented by the redox equilibrium against oxidative stress. In this study, a method for intracellular thiol quantification using HPLC-fluorescence detection was developed. Thiols were derivatized with a thiol-specific fluorescence derivatization reagent, viz. ammonium 7-fluoro-2,1,3-benzoxadiazole-4-sulfonate (SBD-F), followed by reversed-phase separation on an InertSustain AQ-C18 column. Six different SBD-thiols (homocysteine, cysteine, cysteinylglycine, γ-glutamylcysteine, glutathione, and N-acetylcysteine as an internal standard) were separated within 30 min using a citric buffer (pH 3.0)/MeOH mobile phase. The calibration curves of all the SBD-thiols had strong linearity (R² > 0.999). Using this developed method, the thiol concentrations of human chronic myelogenous leukemia K562 cell samples were found to be 5.5–153 pmol/1 × 10⁶ cells. The time-dependent effect of a thiol scavenger, viz. N-ethyl maleimide, on intracellular thiol concentrations was also quantified. This method is useful for elucidating the role of intracellular sulfur metabolism.     

Ocular Delivery of Polyphenols: Meeting the Unmet Needs

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.     

Combinatorial Therapeutic Effect of Inhibitors of Aldehyde Dehydrogenase and Mitochondrial Complex I,and the Chemotherapeutic Drug,Temozolomide against Glioblastoma Tumorspheres

Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action.     

Preliminary Investigation of the Antioxidant,Anti-Diabetic,and Anti-Inflammatory Activity of Enteromorpha intestinalis Extracts

Marine algae are a promising source of potent bioactive agents against oxidative stress, diabetes, and inflammation. However, the possible therapeutic effects of many algal metabolites have not been exploited yet. In this regard, we explored the therapeutic potential of Enteromorpha intestinalis extracts obtained from methanol, ethanol, and hexane, in contrasting oxidative stress. The total phenolic (TPC) and flavonoids (TFC) content were quantified in all extracts, with ethanol yielding the best values (about 60 and 625 mg of gallic acid and rutin equivalents per gram of extract, respectively). Their antioxidant potential was also assessed through DPPH^•, hydroxyl radical, hydrogen peroxide, and superoxide anion scavenging assays, showing a concentration-dependent activity which was greater in the extracts from protic and more polar solvents. The α-amylase and α-glucosidase activities were estimated for checking the antidiabetic capacity, with IC₅₀ values of about 3.8 µg/mL for the methanolic extract, almost as low as those obtained with acarbose (about 2.8 and 3.3 µg/mL, respectively). The same extract also showed remarkable anti-inflammatory effect, as determined by hemolysis, protein denaturation, proteinase and lipoxygenase activity assays, with respectable IC₅₀ values (about 11, 4, 6, and 5 µg/mL, respectively), also in comparison to commercially used drugs, such as acetylsalicylic acid.