Search Results (73)

Background/objectives: Cellular senescence is a hallmark of aging that contributes to tissue dysfunction and age-related diseases. This process is characterized by the activation of the cyclin-dependent kinase inhibitor p16^INK4A and the secretion of pro-inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). In this study, we used human lung-derived cells, including A549 and IMR90 fibroblasts, to identify bioactive compounds from the roots of Liquidambar formosana that suppress p16^INK4A activity and attenuate SASP expression. Methods: Bioactivity-guided isolation was performed to obtain target compounds. The structures of the new compounds were elucidated using extensive 1D and 2D NMR spectroscopic analyses as well as high-resolution mass spectrometry. All isolated compounds were evaluated for their ability to inhibit p16^INK4A, a key regulator of the cell cycle and an important tumor suppressor protein. Results: Two previously undescribed monoterpenoids (1 and 2), characterized as cinnamic acid esters with a monoterpene-derived core, were isolated from the roots of L. formosana, along with six known compounds (3–8). Notably, compound 3 exhibited promising inhibition of p16^INK4A with an IC₅₀ value of 3.9 μM. Furthermore, this compound attenuated the senescence phenotype, as demonstrated by β-galactosidase staining and RT-qPCR analysis. This represents the first report identifying bioactive monoterpenoids from L. formosana that inhibit aging-related biomarkers such as p16^INK4A. Conclusions: These results suggest that cinnamic acid-conjugated monoterpenoids may serve as interesting lead structures for the development of agents targeting the p16^INK4A pathway for the treatment of aging-associated diseases. Further studies will be required to clarify the mechanisms of action of this compound and to evaluate its in vivo efficacy. Full article

UV radiation is responsible for acute and chronic adverse effects on the skin. In recent years, it has been shown that various phenolic acids, particularly cinnamic acid derivatives, prevent some of these effects. In the present study, the design and synthesis of three esters of ferulic acid, analogues of the octyl methoxycinnamate (OMC), one of the most commercially used filters, are presented. The esters were evaluated for their photoprotective activity against UVA and UVB radiation. The ester 3b exhibited an SPF of 9.22 and a λ_c value of 343.9, higher than the values of OMC (SPF value: 8.19, λ_c value: 337.7). The development and optimization of a novel encapsulation process of the synthesized esters in nanostructured lipid carriers (NLCs) and coating of the NLCs with chitosan was also performed. The optimization of the coating processes was performed using a Box–Behnken experimental design. The optimal nanosystems exhibited a size of 117.0 ± 5 nm, enhanced stability in dispersion, and 78% encapsulation efficiency. The nanoparticles were characterized by ATR/FT–IR, TGA, and TEM. Incorporation of the nanoparticle dispersions in a sunscreen formulation increased the SPF factor of the formulation up to 48%. The esters and nanosystems also showed a satisfactory ability to inhibit the peroxidation of linoleic acid (AAPH induced lipid peroxidation assay) (74–91% inhibition). Full article

Sinomenine has long been known as an anti-inflammatory drug, while poor efficiency and large-dose treatment had limited its further application. Five novel sinomenine 1-Br-4-cinnamic acid esters derivatives 2a–2e were designed and synthesized to improve its analgesic and anti-inflammatory activity. All synthesized sinomenine derivatives were structurally confirmed by NMR and ESI-MS. Molecular docking results showed that compounds 2a–2e had stable binding to the GBP5 protein. The compounds 2a–2e showed stable binding to the GBP5 protein by molecular docking Pre-preparing the druggability of compounds 2a–2e by ADEMT 3.0 showed that each derivative had similar druggability to sinomenine. The analgesic activity of compounds 2a–2e was preliminarily determined by hot plate and acetic acid writhing experiments, while anti-neuroinflammatory effects were evaluated by a xylene-induced mouse ear edema model. The results of the hot plate method showed that the synthesized sinomenine derivatives 2a–2e had some analgesic effects. The results of the acetic acid writhing test showed that the analgesic effects of 2a, 2c, 2e were better than that of sinomenine, and the other derivatives were equivalent to sinomenine. Compound 2b showed excellent anti-inflammatory properties in mouse ear edema. Full article

‘Asprinio’ grape is used to produce a white wine from the Campania region, known as ‘Asprinio’ (DOC since 1993). A plethora of approaches was adopted to characterize the organic compounds (e.g., free amino acids and other metabolites) and microbial population (bacteria and fungi) in ‘Asprinio’ grape must by collecting samples from three different vineyards cultivated with the ‘alberata’ training system. The average free amino acid content of ‘Asprinio’ grape must showed quantitative variations, but no significant statistical differences were found. On average, proline was the most abundant free amino acid (~282 mg/L; 47.9%), followed by arginine (~66 mg/L; 11.5%) and glutamine (~25.2 mg/L; 4.2%). On the other hand, the total polyphenol content (TPC) of ‘Asprinio’ grape must was different, like their antioxidant activity, which increased when the TPC content was higher. Moreover, 1D and 2D NMR spectra highlighted the presence of high sugars amount (in particular glucose) as well as trans-caftaric acid, trans-coutaric acid, trans-fertaric acid, and the cis-isomers of these cinnamate esters. Finally, the evaluation of the microbial communities in the ‘Asprinio’ grape must revealed the presence of several representative bacterial phyla—mainly Bacteroidota, Proteobacteria, and Actinobacteriota—as well as various fungal genera, including Cladosporium, Hanseniaspora, Aspergillus, and Saccharomyces. Notably, these microorganisms, which contribute to the fermentation process and influence the final wine flavor, have been found in different proportions in the grape musts analyzed. Our results contribute to increasing knowledge of the ‘Asprinio’ grape, an indigenous vine of Southern Italy. Full article

Novel derivatives of valproic acid with biologically active moieties, such as thiomorpholine, 4-aminopyridine, serine methyl ester, trolox and the cinnamic acid derivative [(E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid], were synthesized at satisfactory yields. The conjugation of these moieties was based on the rationale of design and evaluation of compounds with selected structural characteristics, aiming at derivatives with multiple targets. These compounds reduced acute inflammation considerably and, in most cases, more than several highly used, well-known, non-steroidal anti-inflammatory drugs. They also offered the inhibition of soybean lipoxygenase, and some of them (compounds 5 and 6) possessed radical scavenging and lipid peroxidation attenuating effects. Their antioxidant capacity was several times higher than that of the established antioxidant trolox. All the tested compounds decreased plasma lipid markers in tyloxapol-induced hyperlipidemia in rats. Compound 2 resulted in 71.1%, 52.8% and 79.1% decrease in total cholesterol, triglycerides and LDL-cholesterol, respectively, at 150 μmol/kg (i.p.). The effect on total and LDL cholesterol is comparable or equal to that of simvastatin, a hypocholesterolemic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor, however, with additionally great triglyceride-decreasing effect compared to simvastatin. Thus, the synthesized compounds may be a valuable addition to multi-functional agents acting against various degenerative disorders that implicate inflammation and lipid derangement. Full article

In this study, we compared different parameters in the ultrasound-assisted extraction of polyphenolic acids from seven parts of Zea mays (kernels, leaves, stems, corn silks, roots, the whole plant, and the whole fermented plant) to identify its richest natural sources. Additionally, the correlation between extraction parameters and polyphenol yield was investigated. The extraction was performed using ultrasound at varying powers (480 or 240 W) and frequencies (80 or 37 kHz). Total phenolic content (TPC) was determined using the Folin–Ciocalteu assay, while radical scavenging activity (RSA) was assessed via the DPPH assay. The TPC values ranged from 0.69 ± 0.00008 mg GAE/g to 4.07 ± 0.0004 mg GAE/g in corn. RSA analysis revealed the highest scavenging activity in corn silk (80.06% ± 1.01) and the lowest in kernels (2.77% ± 0.90). High-performance liquid chromatography identified up to 22 different phenolic acids per sample, with the 5 most abundant being chlorogenic acid, protocatechuic acid ethyl ester, quercetin, sinapic acid, and trans-cinnamic acid. The study found small effects of power and frequency on the extraction efficiency. This suggests a practical advantage for industrial-scale applications, as using 240 W instead of 480 W under the same conditions can reduce energy consumption without compromising yield. Full article

Over the past 130 years, Fischer-Speier esterification has been established as the benchmark method for synthesizing esters from organic acids and alcohols. The reaction’s versatility, arising from the vast combinations of starting materials and the numerous catalytic alternatives to the traditional H₂SO₄, has maintained its relevance, with a steady flow of publications addressing new developments. This review highlights the most significant contributions to Fischer-Speier esterification over the past five years, with a particular emphasis on mechanistic advancements and innovative catalytic systems. Both homogeneous and heterogeneous catalytic approaches are discussed, including novel catalysts leveraging hydrogen-bonding interactions and systems offering fresh insights into specific reaction mechanisms and atypical methodologies. Some of these catalytic systems, as ionic liquids or sulfonated heterogeneous catalytic precursors, reached excellent yields (>90%), e.g., in the synthesis of fatty acids methyl esters. Also, classic catalysts such as H₂SO₄ and para-toluen sulfonic acid were optimized for quantitative conversions (e.g., in the esterification of trans-cinnamic acid with methanol). A consistent number of catalysts was studied with model substrates (as benzoic acid in combination with methanol, ethanol, and ethylene glycol), and new activation pathways were presented. Full article

Cinnamic acid and its natural derivatives were primarily used in cosmetics as fragrance materials as well as skin and hair conditioners. Nowadays, not only natural but also synthetic cinnamic acid derivatives are used as active ingredients of cosmetic formulations. They still serve as fragrance ingredients but also as active ingredients supporting the treatment of selected dermatoses such as acne vulgaris, atopic dermatitis, and hyperpigmentation. They are also commonly used in anti-aging cosmetic formulations. On the other hand, several cinnamic acid derivatives used as fragrances in cosmetic products are classified as potential allergens which can cause contact dermatitis. The main mechanisms of action proved for various cinnamic acid derivatives include antioxidant, antimicrobial, anti-inflammatory, and antimelanogenic properties. Most commonly used cinnamic acid derivatives in cosmetics products are hydroxy acids such as ferulic acid, caffeic acid, p-coumaric acid, and sinapic acid. Chemical synthesis led to several modified acids, esters, and amides, which also showed the potential to be used in cosmetic formulations. Full article

Natural alkylated hydroxy cinnamates (AHCs) isolated from medicinal plants and the thereby designed and synthesized cinnamides are derivatives of hydroxy cinnamic acids such as p-coumaric, sinapic, ferulic, and caffeic acids, which are naturally derived from human dietary sources. The pharmacological properties displayed by AHCs based on their inherent structure range include antioxidant, antimicrobial, antiplasmodial, anti-tyrosinase, Alzheimer’s and Parkinson’s disease therapy, anticancer therapy, metabolic disease therapy, and biopesticides, which have not been reviewed together. Based on their inherent antioxidant, antimicrobial, and UV absorption and their structure–activity relationships, these cinnamyl esters and amides can be used for food preservation in emulsions and oils, as sun-protective components of skin care formulations, and in many other multifunctional applications. In conclusion, the fine-tuning of the structural features such as the type of hydroxy cinnamic acid used, the length of alkyl chains for variable lipophilicity, conversion from cinnamic to propanoic for antioxidants, the increase in methoxy or the change to amino groups to increase the molar absorption coefficient and loss of absorption values, the substitution by halides or amino groups for potent biopesticides, and conversion from esters to amide bonds leads to different AHCs for biomedical, cosmetic, and agriculture applications as an emerging field of investigation that can overall provide natural, safe, biodegradable, and sustainable molecules. Full article

Antibiotics are currently used for the treatment of Helicobacter pylori (H. pylori), which is confirmed to be the major cause of gastric disorders. However, the long-term consumption of antibiotics has already caused antibiotic resistance and side effects in vivo. Therefore, there is an emerging need for searching for safe and effective anti-H. pylori agents. Inspired by the excellent bioactivities of cinnamic acid, a series of cinnamic acid derivatives (compounds 1–30) were synthesized and determined for H. pylori inhibition. The initial screening revealed that compound 23, a 2,4-dinitro cinnamic acid derivative containing 4-methoxyphenol, showed excellent H. pylori inhibition with an MIC value of 4 μM. Further studies indicated that compound 23 showed anti-bacterial activity and had a bactericidal effect on H. pylori due to the destruction of the bacterial structure. Molecular docking analysis revealed that the 2,4-dinitro groups in cinnamic acid moiety formed hydrogen bonding with amino acid residues in an active pocket of H. pylori protein. Interestingly, the ester moiety fitted into the hydrophobic pocket, attaining additional stability to compound 23. Above all, the present study reveals that compound 23 could be considered a promising anti-H. pylori agent to treat H. pylori causing gastritis. Full article

Phenylpropanoid sucrose esters are a large and important group of natural substances with significant therapeutic potential. This work describes a pilot study of the enzymatic hydroxycinnamoylation of sucrose and its derivatives which was carried out with the aim of obtaining precursors of natural phenylpropanoid sucrose esters, e.g., vanicoside B. In addition to sucrose, some chemically prepared sucrose acetonides and substituted 3′-O-cinnamates were subjected to enzymatic transesterification with vinyl esters of coumaric, ferulic and 3,4,5-trimethoxycinnamic acid. Commercial enzyme preparations of Lipozyme TL IM lipase and Pentopan 500 BG exhibiting feruloyl esterase activity were tested as biocatalysts in these reactions. The substrate specificity of the used biocatalysts for the donor and acceptor as well as the regioselectivity of the reactions were evaluated and discussed. Surprisingly, Lipozyme TL IM catalyzed the cinnamoylation of sucrose derivatives more to the 1′-OH and 4′-OH positions than to the 6′-OH when the 3′-OH was free and the 6-OH was blocked by isopropylidene. In this case, Pentopan reacted comparably to 1′-OH and 6′-OH positions. If sucrose 3′-O-coumarate was used as an acceptor, in the case of feruloylation with Lipozyme in CH₃CN, 6-O-ferulate was the main product (63%). Pentopan feruloylated sucrose 3′-O-coumarate comparably well at the 6-OH and 6′-OH positions (77%). When a proton-donor solvent was used, migration of the 3′-O-cinnamoyl group from fructose to the 2-OH position of glucose was observed. The enzyme hydroxycinnamoylations studied can shorten the targeted syntheses of various phenylpropanoid sucrose esters. Full article

Gelsemium sempervirens (L.) J.St.-Hil. is an evergreen shrub occurring naturally in North and Middle America. So far, more than 120 alkaloids have been identified in this plant in addition to steroids, coumarins and iridoids, and its use in traditional medicine has been traced back to these compound classes. However, a comprehensive phytochemical investigation of the plant with a special focus on further compound classes has not yet been performed. Therefore, the present study aimed at an extensive HPLC-MSⁿ characterization of secondary metabolites and, for the first time, reports the occurrence of various depsides and phenolic glycerides in G. sempervirens roots and rhizomes, consisting of benzoic and cinnamic acid derivatives as well as dicarboxylic acids. Furthermore, mono- and disaccharides were assigned by GC-MS. Applying the Folin–Ciocalteu assay, the phenolic content of extracts obtained with different solvents was estimated to range from 30 to 50% calculated as chlorogenic acid equivalents per g dry weight and was related to the DPPH radical scavenging activity of the respective extracts. Upon lactic acid fermentation of aqueous G. sempervirens extracts, degradation of phenolic esters was observed going along with the formation of low-molecular volatile metabolites. Full article

Cancer is a global health problem, with the incidence rate estimated to reach 40% of the population by 2030. Although there are currently several therapeutic methods, none of them guarantee complete healing. Plant-derived natural products show high therapeutic potential in the management of various types of cancer, with some of them already being used in current practice. Among different classes of phytocompounds, pentacyclic triterpenoids have been in the spotlight of research on this topic. Ursolic acid (UA) and its structural isomer, oleanolic acid (OA), represent compounds intensively studied and tested in vitro and in vivo for their anticancer and chemopreventive properties. Since natural compounds can rarely be used in practice as such due to their characteristic physico-chemical properties, to tackle this problem, their derivatization has been attempted, obtaining compounds with improved solubility, absorption, stability, effectiveness, and reduced toxicity. This review presents various UA and OA derivatives that have been synthesized and evaluated in recent studies for their anticancer potential. It can be observed that the most frequent structural transformations were carried out at the C-3, C-28, or both positions simultaneously. It has been demonstrated that conjugation with heterocycles or cinnamic acid, derivatization as hydrazide, or transforming OH groups into esters or amides increases anticancer efficacy. Full article

There is a significant trend towards the integration of natural substances with bio-polymers for fully bio-based functional composites. Polylactic acid is regarded as a promising biodegradable polymer for replacing synthetic polymers. Differing from the case of natural fiber, the incompatibility of polylactic acid with bio-based molecules prevents it from being used to fabricate high-quality sustainable composites. This work presents a simultaneous ultraviolet shielding and antibacterial finishing process of polylactic acid combined with bioactive baicalin and an eco-friendly ester, which is highlighted for (a) the lack of synthetic chemicals involved in such process, (b) adsorption enhancement achieved at a mild temperature, and (c) marginal color change on treated polylactic acid. A response surface methodology was adopted to analyze the impacts of various factors on the baicalin quantity in polylactic acid, and to optimize the treatment condition. The uptake ratio of baicalin in polylactic acid was drastically promoted from 8.5 mg/g to 21.1 mg/g using methyl cinnamate. The response surface methodology based on a central composite design experiment indicated that the usage of baicalin was the most significant factor followed by methyl cinnamate and temperature. After optimization, a very faint color depth of 1.2 was apparent, but UPF 50+ and 92% bacterial reduction could be achieved. In all, the success in strengthening of the functionalities of polylactic acid extends the applications of polylactic acid products. Full article

Fifteen amine derivatives of cinnamic acid were synthesized by reaction of the corresponding benzaldehydes and malonic acid. The selected acids were then converted into methyl esters. Three esterification methods were tested with (1) thionyl chloride in methanol, (2) sulfuric acid in methanol, and (3) dimethyl sulfate in acetone. The latter method turned out to be the best, both in terms of reaction efficiency and product purity. The chemical structure and purity of all the synthesized compounds were verified by elemental analysis, ¹H and ¹³C NMR, and IR spectroscopy. The cinnamic acids and their esters, thanks to an extensive system of conjugated double bonds compared to analogous benzoic acids, can be used to obtain dyes for various applications, including non-linear optics and optoelectronics. Therefore, their basic spectroscopic properties are presented as well. Full article