Synthetic Activity Research Articles

Comparative histological assessment of the effect of retinol palmitate preparations on aging skin

Background: Most often, the natural form of vitamin A (retinol palmitate) is used to prevent skin aging. There are two topical drugs on the Russian market that contain a high concentration of retinоl palmitate. This is the ointment "Videstim", which contains 0.5% retinol palmitate and ointment "RadevitАctive", which in addition to 1% retinol palmitate also includes cholecalciferol (0.005%) and tocopherol acetate (0.5%). The specific effects of these drugs on the structure of aging skin have not yet been fully studied. Aims: Comparative histological assessment of the effects of "Videstim" ointment and "RadevitАctive" ointmenton the epidermis and dermis of woman aged 40-55 years old. Materials and methods: The clinical study included 18 women aged 40 to 55 years old. Group I included 6 women who used "Videstim" ointment 2 times a day on the skin of the face. Group II consisted of 6 women who used "RadevitАctive" ointment 2 times a day on the skin of the face. Group III consisted of 6 women and was an intact comparison group. The observation period is 90 days. Patients underwent a punch biopsy with with histological examination of the skin before and after 90 days of using of the aforementioned drugs. Results: According to the results of the study, it was revealed that "Videstim" and "RadevitАctive" ointments they have a stimulating effect on the proliferation of keratinocytes of the epidermis, which manifested itself in an in increasing the number of rows of cells of the prickly layer. In addition, under the action of these drugs, the synthetic activity of keratinocytes of the granular layer increases, which contributes to the proper formation of the stratum corneum of the epidermis.. The use of ointments leads to a significant increase in the thickness of both the granular and prickly layers of the epidermis and the dermis. Conclusions: Ointments with a high concentration of retinol palmitate improve the structure of aging skin.

ETHOS.ActivityAssure—an open-source validation framework for synthetic European activity profiles

The simulation of human behavior is an essential component in the domain of energy demand modeling. However, due to its diverse nature, it is often unclear whether a simulated behavior pattern is fitting to certain contexts. Combined with the poor availability of appropriate activity data, this makes proper validation of behavior models difficult. Existing validation approaches are limited and specialized to the respective use case, and are therefore not reusable or comparable. To address this issue, the new open-source framework ETHOS.ActivityAssure is presented for evaluation of generated activity profiles, supporting the validation of behavior models. For this purpose, an aggregated activity dataset is created from restricted European time use data and published to ensure reusability. Validation is conducted through a set of indicators and comparative plots, taking into account activity duration, frequency, and time. A categorization of person types and activities enables mapping to result categories commonly used in behavior models. The framework's capabilities are demonstrated on the residential demand model LoadProfileGenerator. The developed framework allows for consistent and reproducible validation of synthetic activity profiles targeting Europe, without requiring access to confidential data. This offers the opportunity to enhance both new and existing behavior models by identifying flaws, compare multiple modeling approaches, and thoroughly evaluate model quality for diverse target purposes.

The synergistic interaction of fungi with different structural characteristics improves the leaching of lithium from lepidolite

The aim of this study was to explore the improvement of lithium leaching from lepidolite by microbial co-culture, focusing on the synergistic effect of different structural fungi in improving the leaching performance of biological systems. The results showed that in the single leaching experiment, the multicellular fungi and the unicellular yeast showed weak effects. Multicellular fungus is limited by insufficient EPS secretion, while unicellular yeast is non-mycelial organisms with weak acid production capacity and limited effect on minerals. However, in the combined leaching experiment, the interspecific collaboration promoted the synthetic and metabolic activity of the two strains, resulting in changes in the type and content of organic acids, polysaccharides, proteins and humus. The content of citric acid reached the highest value of 16.98g·L-1 at about 22 d, and the EPS secreted by unicellular yeast promoted the mycelium adhesion and mineral wrapping of multicellular fungi. The combined action of the two enhanced the effects of acidification, complexation and mycelium destruction, and improved the leaching effect. This study revealed the synergistic metabolic mechanism of lepidolite leaching by fungi with different structures, verified the effectiveness of microbial co-culture to improve the leaching rate, and provided a basis for industrial application. In addition, the use of co-culture technology has a positive impact on commercial production and environmental protection.

Quinoline-hydrazone Conjugates: Recent Insights into Synthetic Strategies, Structure-activity Relationship, and Biological Activities

: The fusion of two distinct and free pharmacologically active chemical moieties into single conjugate molecules can result in synergized pharmacological action of both moieties into the new composite molecule. Ultimately, it increases the therapeutic potentialof the newly formed hybrid compound which is more than the combination of each specific moiety’s therapeutic potential. So nowadays, it is common practice to combine at least two pharmacophores to create a particular compound with a powerful therapeutic effects. Quinoline has been reported with multiple pharmacological activities and industrial applications. On the other hand, hydrazones are also found very useful as herbicides, acaricides, rodenticides, insecticides, and various therapeutic applications. The conjugate containing quinoline and hydrazone is also being used as an anticancer, antibacterial, antifungal, antimalarial, anticonvulsant, anti-inflammatory, and antioxidant. The combination of two moieties yields a better therapeutic effect because of excellent efficacy and fewer side effects. Several synthetic methods have been employed in recent times to synthesize quinoline-hydrazone conjugates which are listed in the manuscript with their merits and demerits. The structure-activity relationship relating to their pharmacological actions with molecular structure has also been highlighted. The article aims to provide a good toolkit and comprehension to the medicinal chemists, for their future work, comprising of quinoline-hydrazone hybrid compounds.

Recent Progress in Synthetic Chemistry and Biological Activities of Pyrimido[ 4,5-b] Quinoline Derivatives (Part III)

Abstract: Amongst heterocyclic compounds, quinoline and pyrimidine are advantaged scaffolds that appear as significant assembly motifs for the development of new drug entities. Moreover, quinolinepyrimidine- inspired hybrids have a number of biological characteristics that are known. In addition, many pyrimido[4,5-b]quinoline ring systems (PyQs4,5-b), specifically concerning medicinal chemistry, have been reported over the past decade. The synthesis of (PyQs4,5-b) using barbituric acid, thiobarbituric acid, pyrimidine, and their derivatives is presented in this review. The preparation of PyQs4,5-b was clarified through the following chemical reactions: Friedländer, Vilsmeier-Haack formylation, Hantzsch-like reaction, and one-pot three-component reaction.

The Anti-Candidal Activity of Salvia verticillata subsp. verticillata Against Several Candida Species

The examination of Salvia verticillata extract encompassed an exploration of its anti-Candida properties, phytochemical composition, antioxidant activity, and the quantification of total tannins. The use of ethanol as a solvent yielded the highest extraction efficiency at 26.1%. The plant exhibited a substantial tannin content of 6.5 mg/kg, signifying a noteworthy concentration. The inhibitory zones against Candida tropicalis reached a minimum diameter of 17.6 mm, while Candida guilliermondii displayed the most significant inhibition with a zone diameter of 21.8 mm. The minor inhibitory concentration (MIC) findings for all Candida species ranged from 6.25 to 12.5 g/ml. In the case of Candida guilliermondii, the synthetic antifungal activity FLU/25 demonstrated a maximal inhibition zone measuring 39.30 mm. Additionally, the maximum antioxidant activity, recorded at 0.3 ml, reached a value of 98.65. Phytochemical screening unveiled elevated concentrations of phenols and flavonoids, with malic acid (1901.1 g/g), hesperidin (302.4 g/g), and rosmarinic acid (30619.93 g/g) all experiencing an increase in concentration. These findings provide a comprehensive understanding of the diverse bioactive components and properties associated with Salvia verticillata extract.

Anti-fibrotic effects of the sirt6-activator mdl-800 in cardiac stromal cells

Abstract Background Epigenetic changes are among the molecular substrates of cellular stress responses and tissue remodeling in heart failure progression. The sirtuin family of NAD+-dependent histone and non-histone protein deacetylases exert a protective anti-fibrotic role by negatively modulating the inflammatory response and by positive regulation of autophagy-related genes. Sirtuin6 (SIRT6) stands out as a key cardiac protector that can mitigate aging-induced cardiomyocyte senescence and cardiac hypertrophy. Cardiac stromal cells (CSCs) play a pivotal role in fibrosis and remodeling, regulating the composition and stiffness of the extracellular matrix (ECM). Autophagy enhancement has anti-fibrotic effects in CSCs, but the specific role of SIRT6 modulation in CSCs remains unexplored. Purpose To investigate the biological effects of MDL-800, a synthetic allosteric SIRT6 activator, on the stress response and fibrotic activation of CSCs. Methods CSCs were isolated from 4-week-old C57Bl6J mice by explant culture and stimulated with 10ng/ml of TGF-beta1 (TGFb1) up to 72h to induce fibrotic activation. CSCs were treated with MDL-800 up to 10µM and up to 72h, analyzed for cell viability, gene and protein expression levels. Results TGFb1 treatment led to a 0.64-fold reduction in SIRT6 gene expression after 24h. The MTS assay was used to assess a viability dose-response to MDL-800 up to 72h of treatment. The non-toxic concentrations of 2.5µM and 5µM were selected for further experiments (2.5µM vs CTR 0.97-fold and 5µM vs CTR 0.92-fold, normalized OD vs t0). Co-treatment of 5µM MDL-800 with TGFb1 for 72h resulted in a dose-dependent decrease in the expression of TGFb1-induced fibroblast activation markers, as confirmed by immunofluorescence staining for aSMA (TGFb1 vs CTR 2.21-fold, p<0.05; 5µM vs TGFb1 0.46-fold, p<0.05, N=4; mean fluorescence intensity). The anti-fibrotic effect mediated by MDL-800 was further validated by real-time PCR indicating a reduction in the mRNA expression of multiple fibrotic markers, including ACTA2 (TGFb1 vs CTR 1.67-fold, 5µM vs TGFB 0.29-fold; N=2), COL1a1 (TGFb1 vs CTR 1.32-fold, 5µM vs TGFb1 0.87-fold; N=2) COL3a1 (TGFb1 vs CTR 1.06-fold, 5µM vs TGFb1 0.43-fold; N=2) and POSTN (TGFb1 vs CTR 6.37-fold, 5µM vs TGFb1 0.23-fold; N=2). Treatment with 5µM MDL-800 demonstrated an increase in SIRT6 gene expression, suggesting a transcriptional modulation (TGFb1 vs CTR 0.95-fold, 5µM vs TGFb1 1.68-fold; N=2). Western Blot analyses showed an increase in protein levels of the autophagosome marker LC3-II following treatment with 5µM MDL-800 (TGFb1 vs CTR 0.95-fold; 5µM vs TGFb1 3.01-fold), suggesting that autophagy enhancement may be a potential mechanism for the observed anti-fibrotic effects. Conclusion MDL-800 treatment in CSCs is associated with a dose-dependent reduction of TGFb1-induced fibrotic markers and to increased levels of the autophagy marker, suggesting its potential use as an anti-fibrotic molecule for the heart.

Dermal fibroblasts in the focus of modern cosmetology: aging and response to cosmetic procedures: A review

The article presents a review of modern information about the structure and function of dermal fibroblasts. The morphophysiology of fibroblasts, their role in the formation of connective tissue of the dermis and its restoration after damage are discussed. Detailed knowledge about proliferative and synthetic activity of fibroblasts seems to be very important in the reasonable choice of methods for correction of age-related skin changes and sequence of invasive procedures.

Kinetic and Mechanistic Studies of Human Oligoadenylate Synthetase 1.

Oligoadenylate synthetase 1 (OAS1) catalyzes the dsRNA-dependent polymerization of ATP to form oligoadenylate, a second messenger of the innate immunity system. This paper reports kinetic and mechanistic studies of OAS1-catalyzed dimerization of ATP to form 2'-5'-diadenylate and pyrophosphate (PPi), the first step in ATP polymerization. Major findings include the following: (1) Reaction progress curves for the production of PPi are biphasic, characterized by a presteady-state lag followed by the linear, steady-state production of PPi. (2) The dependence of steady-state velocity on ATP concentration is sigmoidal and can be described by a rate law derived for a mechanism involving enzyme-catalyzed substrate dimerization. (3) Steady-state velocities were determined as a function of ATP concentration at fixed concentrations of poly(I:C), a synthetic dsRNA activator of OAS1. The data suggest a random mechanism in which either ATP or poly(I:C) can add first to the enzyme. (4) The dependence of klag on poly(I:C) and ATP concentration requires expansion of this mechanism to include slow conformational isomerization of various poly(I:C)- and ATP-bound complexes of inactive OAS1 to form complexes comprising an active enzyme, to ultimately form the reactive Michaelis complex of active OAS1, poly(I:C), and two molecules of ATP. Finally, within this complex, the two molecules of ATP dimerize to form 2'-5'-diadenylate and pyrophosphate. (5) The pH dependence and solvent deuterium isotope effect for kcat suggests that proton transfer occurs in the rate-limiting transition state, which likely involves proton abstraction from the 2'-hydroxyl of the adenylate acceptor ATP as the oxygen of this hydroxyl attacks the a-phosphate of the adenylate donor ATP in an SN2 fashion.

GABA(A) Receptor Activation Drives GABARAP-Nix Mediated Autophagy to Radiation-Sensitize Primary and Brain-Metastatic Lung Adenocarcinoma Tumors.

In non-small cell lung cancer (NSCLC) treatment, radiotherapy responses are not durable and toxicity limits therapy. We find that AM-101, a synthetic benzodiazepine activator of GABA(A) receptor, impairs the viability and clonogenicity of both primary and brain-metastatic NSCLC cells. Employing a human-relevant ex vivo 'chip', AM-101 is as efficacious as docetaxel, a chemotherapeutic used with radiotherapy for advanced-stage NSCLC. In vivo, AM-101 potentiates radiation, including conferring a significant survival benefit to mice bearing NSCLC intracranial tumors generated using a patient-derived metastatic line. GABA(A) receptor activation stimulates a selective-autophagic response via the multimerization of GABA(A) receptor-associated protein, GABARAP, the stabilization of mitochondrial receptor Nix, and the utilization of ubiquitin-binding protein p62. A high-affinity peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis that triggers autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.

Structure-Aided Computational Design of Triazole-Based Targeted Covalent Inhibitors of Cruzipain.

Cruzipain (CZP), the major cysteine protease present in T. cruzi, the ethiological agent of Chagas disease, has attracted particular attention as a therapeutic target for the development of targeted covalent inhibitors (TCI). The vast chemical space associated with the enormous molecular diversity feasible to explore by means of modern synthetic approaches allows the design of CZP inhibitors capable of exhibiting not only an efficient enzyme inhibition but also an adequate translation to anti-T. cruzi activity. In this work, a computer-aided design strategy was developed to combinatorially construct and screen large libraries of 1,4-disubstituted 1,2,3-triazole analogues, further identifying a selected set of candidates for advancement towards synthetic and biological activity evaluation stages. In this way, a virtual molecular library comprising more than 75 thousand diverse and synthetically feasible analogues was studied by means of molecular docking and molecular dynamic simulations in the search of potential TCI of CZP, guiding the synthetic efforts towards a subset of 48 candidates. These were synthesized by applying a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) centered synthetic scheme, resulting in moderate to good yields and leading to the identification of 12 hits selectively inhibiting CZP activity with IC50 in the low micromolar range. Furthermore, four triazole derivatives showed good anti-T. cruzi inhibition when studied at 50 μM; and Ald-6 excelled for its high antitrypanocidal activity and low cytotoxicity, exhibiting complete in vitro biological activity translation from CZP to T. cruzi. Overall, not only Ald-6 merits further advancement to preclinical in vivo studies, but these findings also shed light on a valuable chemical space where molecular diversity might be explored in the search for efficient triazole-based antichagasic agents.

Synthetic Optimization and Antibacterial Activity of Novel Benzodioxepine-Biphenyl Amide Derivatives.

The biosynthesis of fatty acids constitutes a critical metabolic pathway in bacterial organisms. Prior investigations have highlighted the synthesis of antimicrobial compounds anchored in the benzodioxepin scaffold, noted for their pronounced antibacterial properties. Leveraging this foundational knowledge, the current research endeavors to meticulously engineer and synthesize a series of eight innovative benzodioxepin amide-biphenyl derivatives. This achievement was realized through the sophisticated optimization of synthetic methodologies. The scope of this study extends to a rigorous evaluation of the antibacterial prowess and biocompatibility of the aforementioned novel derivatives. Notably, Compound E4 emerged as a supremely potent antimicrobial agent. A detailed elucidation of the crystalline architecture of Compound E4 was conducted, alongside a thorough docking study to explore its interactions with the FabH enzyme.

Crystal Structure of the Monocarborane Magnesium(II) Acetylide and Its Use in the Synthesis of α,β-Unsaturated Ketones.

We report the first crystal structure of heteroleptic Grignard reagent 2 based on the carborane endo/exo dianion [CB11H11-12-C≡C]2-. Full characterization reveals a rare coordination pattern and affirms the bimetallic nature. Navigating the reactivity landscape, we unlock the potential of 2 in nucleophilic addition with ketones to afford propargylic alcohols 3, renowned for their synthetic versatility and potential biological activities, and unveil the Meyer-Schuster rearrangement, yielding α,β-unsaturated carbonyl compounds 4. This narrative of synthesis, characterization, and reactivity opens new horizons for carborane chemistry, offering avenues for innovation and facile functionalization of carborane scaffolds.

An In‐Depth Review on Recent Progress in Synthetic Approaches and Biological Activities of Thiazol‐2(3H)‐Imine Derivatives

AbstractThis review presents the in‐dept analysis of the synthetic approaches towards thiazol‐2(3H)‐imine and embarks at its various biological properties published during 2000 to 2023. The most important method of synthesis involves the reaction of substituted thioureas and α‐halo carbonyl compounds, and condensation and nucleophilic addition of 2‐amino‐1,3‐thiazoline with aldehydes. Additionally, isothiocyanate‐based multicomponent synthesis, and α‐nitroepoxides have been proved as benign precursors for this motif. Several eco‐friendly and solvent‐free synthesis from diazonium salts, acetylenes, tertiary enaminones and thiosemicarbazides have also been reported. This epitome is a unique combination of synthetic methods as well as biological activities like anti‐inflammatory, anti‐bacterial, anti‐cancer, anti‐leishmanial, anti‐microbial, herbicidal, anti‐HIV, and may be a valuable tool for researchers to tailor the synthetic procedures according to specific target structures and applications. Moreover, this review enlightens the applications of thiazol‐2(3H)‐imine as platelet GPIIB/IIIA receptor antagonists, alkaline phosphatase inhibitors, neurodegenerative drug Pifithrin‐α analogues, and skin whitening agents.

Experience: A Comparative Analysis of Multivariate Time-Series Generative Models: A Case Study on Human Activity Data

Human activity recognition (HAR) is an active research field that has seen great success in recent years due to advances in sensory data collection methods and activity recognition systems. Deep artificial intelligence (AI) models have contributed to the success of HAR systems lately although still suffering from limitations such as data scarcity, the high costs of labelling data instances and datasets’ imbalance and bias. The temporal nature of human activity data, represented as time series data, impose an additional challenge to using AI models in HAR because most state-of-the-art models do not account for the time component of the data instances. These limitations have inspired the time-series research community to design generative models for sequential data but very little work has been done to evaluate the quality of such models. In this work, we conduct a comparative quality analysis of three generative models for time-series data, using a case study in which we aim to generate sensory human activity data from a seed public dataset. Additionally, we adapt and clearly explain four evaluation methods of synthetic time-series data from the literature and apply them to assess the quality of the synthetic activity data we generate. We show experimentally that high quality human activity data can be generated using deep generative models, and the synthetic data can thus be used in HAR systems to augment real activity data. We also demonstrate that the chosen evaluation methods effectively ensure that the generated data meets the essential quality benchmarks of realism, diversity, coherence and utility. Our findings suggest that using deep generative models to produce synthetic human activity data can potentially address challenges related to data scarcity, biases, and expensive labeling. This holds promise for enhancing the efficiency and reliability of HAR systems.

Fluorinated plant activators induced dual-pathway signal transduction and long-lasting ROS burst in chloroplast

Synthetic plant activators represent a promising novel class of green pesticides that can triggering endogenous plant immunity against pathogen invasion. In our previous study, we developed a series of fluorinated compounds capable of eliciting disease resistance in plants; however, the underlying regulatory mechanisms remained unclear. In this study, we systematically investigated the mechanism of plant immune activation using four synthetic plant activators in Arabidopsis thaliana (A. thaliana), including two fluorine-substituted and two non‑fluorine-substituted molecules. Our findings revealed that the fluorinated compounds exhibited superior disease resistance activity compared to the non-fluorinated molecules. Gene expression analysis in systemic acquired resistance (SAR)- and induced systemic resistance (ISR)-related pathways demonstrated that fluorine substitution effectively regulated both SAR- and ISR-pathway activation, highlighting the distinct roles of fluorine in modulating the plant immune system. Notably, the prolonged ROS burst was observed in chloroplasts following treatment with all four plant activators, contrasting with the transient ROS burst induced by natural elicitors. These results provide insights into the unique mechanisms underlying synthetic plant activator-induced plant immunity. Furthermore, comprehensive proteomic analysis revealed a robust immune response mediated by fluorine-substituted plant activators. These findings offer novel insights into the role of fluorine substitution in SAR- and ISR-associated immune signaling pathways and their distinct impact on ROS production within chloroplasts.

Mechanism of Antimicrobial Activities of Medicinal Plants Extracts, From Traditional Knowledge to Scientific Insights

Background: Over the years, the medicinal properties of plants have been recognized as important sources of active ingredients in herbal medicine. In particular, plant-derived active ingredients have been used in microbial natural products long before the advent of modern medicine. Discussion: Since ancient times, the potency of medicinal plant products has been linked to the chemical, biochemical and synthetic activities of the plant product. Therefore, with the advancement of modern science in molecular and cellular biology, analytical chemistry and pharmaceuticals, the unique properties of these plant products are used to exploit the chemical and structural diversity and diversity. of the biology of this type of fruit in relation to their medicinal properties. Conclusion: New molecules are of interest to drug designers who are interested in modifying the chemical entities or structural parameters of natural products to produce new molecules that can be made into effective medicine.

Quantitative structure-insecticidal activity of essential oils on the human head louse (Pediculus humanus capitis)

ABSTRACT In the search for natural and non-toxic products alternatives to synthetic pesticides, the fumigant and repellent activities of 35 essential oils are predicted in the human head louse (Pediculus humanus capitis) through the Quantitative Structure-Activity Relationships (QSAR) theory. The number of constituents of essential oils with weight percentage composition greater than 1% varies from 1 to 15, encompassing up to 213 structurally diverse compounds in the entire dataset. The 27,976 structural descriptors used to characterizing these complex mixtures are calculated as linear combinations of non-conformational descriptors for the components. This approach is considered simple enough to evaluate the effects that changes in the composition of each component could have on the studied bioactivities. The best linear regression models found, obtained through the Replacement Method variable subset selection method, are applied to predict 13 essential oils from a previous study with unknown property data. The results show that the simple methodology applied here could be useful for predicting properties of interest in complex mixtures such as essential oils.

Features of reactions to stress in rats with passive-defense behavior after light desynchronosis and physical activity

An assessment was made of hematological parameters of peripheral blood and structural and functional changes in the adrenal glands in stress-unresistant rats (passive-defensive type of behavior in the open field test) after exposure to light deprivation and physical activity during the spring equinox. The experiment showed that light deprivation for 10 days reduces the total number of leukocytes, the absolute content of monocytes, granulocytes, lymphocytes and the level of corticosterone in the peripheral blood compared to the intact group, that was on a natural lighting regime. Histological analysis of the adrenal glands of this group showed, that in the zona fasciculata under such conditions there was nuclear hypertrophy, an increase in the nuclear-cytoplasmic ratio of adrenocorticocytes and a decrease in the size of the zona glomerulosa of the adrenal cortex of rats in relation to the intact group. Physical activity in the form of forced swimming until complete fatigue for 5 days in a row in natural light in stress-unresistant rats did not change the parameters of the peripheral blood of animals, however it led to an increase in the area of the cytoplasm, the nuclear-cytoplasmic ratio, as well as the formation of hypertrophy of the nuclei of adrenocorticocytes in the fascicle adrenal zones, which indicated the preparation of cells for increased synthetic activity. Keeping rats for 10 days in complete darkness before forced swimming every day for 5 days, on the one hand, formed a hypoxic state and exhaustion of the adrenal glands, on the other hand, stabilized the leukocyte pool of peripheral blood compared to similar indicators in intact rats.

Hydroxytyrosol isolation, comparison of synthetic routes and potential biological activities.

Hydroxytyrosol (HT) is a polyphenol found in the olive plant (Olea europaea) that has garnered attention from the food, feed, supplement, and pharmaceutical industries. HT has evolved from basic separation and extraction to chemical and biocatalytic synthesis. The yield of HT can reach 1.93 g/L/h through chemical synthesis and 7.7 g/L/h through biocatalysis; however, both methods are subject to inherent limitations. Furthermore, the potential health benefits associated with HT have been highlighted, including its ability to act as an antioxidant, reduce inflammation, combat cancer and obesity, and exert antibacterial and antiviral effects. Its neuroprotective effects, skin protection, and wound healing capabilities are also discussed. Given these remarkable biological properties, HT stands out as one of the most extensively investigated natural phenols. This review highlights future methods and pathways for the synthesis of HT, providing insights based on its bioactivity characteristics, health benefits, and potential future applications.