Molecules

19 pages, 1960 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Ramalin Derivatives as Multi-Target Agents for Alzheimer’s Disease

by Tai Kyoung Kim, Ju-Mi Hong, Yongeun Cho, Yeji Jeon, Heewon Cho, Jeongmi Lee, Jaewon Kim, Kyung Hee Kim, Il-Chan Kim, Se Jong Han, Hyuncheol Oh, Dong-Gyu Jo and Joung Han Yim

Molecules 2025, 30(9), 2030; https://doi.org/10.3390/molecules30092030 (registering DOI) - 2 May 2025

Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives and evaluated their therapeutic potential against AD, focusing on antioxidant, anti-inflammatory, and neuroprotective [...] Read more.

Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by cognitive decline, oxidative stress, neuroinflammation, amyloid-beta (Aβ) accumulation, and tau protein hyperphosphorylation. In this study, we synthesized novel Ramalin derivatives and evaluated their therapeutic potential against AD, focusing on antioxidant, anti-inflammatory, and neuroprotective activities. RA-2OMe, RA-4OMe, RA-2CF3, and RA-4OCF3 showed strong antioxidant effects, while RA-2OMe exhibited potent NO and NLRP3 inhibition (~20%). RA-NAP, RA-PYD, and RA-2Q showed moderate anti-inflammatory activity. BACE-1 inhibition was significant in RA-3CF3, RA-NAP, and RA-PYD, with IC₅₀ values lower than that of positive control, indicating greater inhibitory potency. RA-NAP and RA-PYD effectively inhibited both Aβ and tau aggregation, highlighting their multi-target potential for AD therapy. These findings indicate that Ramalin derivatives exhibit potential for multi-target activity in AD treatment. However, further studies on their pharmacokinetics, in vivo efficacy, and long-term safety are required to confirm their therapeutic applicability. Full article

(This article belongs to the Section Organic Chemistry)

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19 pages, 2916 KiB

Open AccessArticle

Nutritional and Functional Values of Grape Seed Flour and Extract for Production of Antioxidative Dietary Supplements and Functional Foods

by Yavor Ivanov, Milka Atanasova and Tzonka Godjevargova

Molecules 2025, 30(9), 2029; https://doi.org/10.3390/molecules30092029 (registering DOI) - 2 May 2025

Abstract

The potential of the seed flours and extracts of the red grapes Pinot Noir and Marselan for application as food additives and antioxidative dietary supplements was determined. The differences between the quality characteristics of the seeds, flour, and extracts of the two grape [...] Read more.

The potential of the seed flours and extracts of the red grapes Pinot Noir and Marselan for application as food additives and antioxidative dietary supplements was determined. The differences between the quality characteristics of the seeds, flour, and extracts of the two grape varieties were examined. The polyphenol composition and antioxidant potential of the two extracts were compared. The extracts were rich in polyphenols, especially flavonoids (52.01 mg QE/g DW) and procyanidins (152.18 mg CE/g DW). The nutritional composition of the flours and extracts was determined. It was found that the content of ash, crude protein, crude fat, and total dietary fibers in the flour from the studied grape seeds was about 1.5 times higher than that in the extracts. Only the carbohydrate content was 2–2.5 times higher in both extracts compared to that in the flours. The content of macro and microelements in the seed extracts and in the flours was high. The inhibitory potential of the two seed extracts on three key enzymes affecting diabetes and obesity—α-amylase, α-glucosidase, and pancreatic lipase—was studied. The highest degree of extract inhibition against α-glucosidase was determined (IC₅₀—2.53 ± 0.24 µg/mL). A real inhibitory assessment of the extracts was made by implementing an in vitro digestion simulation method. It was found that the percentage of inhibition of the enzymes with the digested extract was higher compared to those with the undigested extract in buffer and salt solution. Our study proves that the high content of flavonoids and procyanidins in the two extracts determines their high inhibitory capacity against the three enzymes and their potential for managing diabetes and obesity. Full article

(This article belongs to the Special Issue Sustainable Use of Grapes and Grape Processing By-Products in the Development of Functional Foods)

15 pages, 10575 KiB

Open AccessArticle

Preparation and Electrochemical Characteristics of the Co-Doped Li₇La₃Zr₂O₁₂ Solid Electrolyte with Fe³⁺ and Bi³⁺

by Jialu Qu, Xingyu Duan, Ke Xue and Shengli An

Molecules 2025, 30(9), 2028; https://doi.org/10.3390/molecules30092028 (registering DOI) - 2 May 2025

Abstract

Solid-state electrolytes (SSEs) have emerged as the most promising alternative to liquid electrolytes in batteries due to their enhanced stability and safety. Among these, the garnet-type Li₇La₃Zr₂O₁₂ (LLZO) solid electrolyte has attracted significant research interest due [...] Read more.

Solid-state electrolytes (SSEs) have emerged as the most promising alternative to liquid electrolytes in batteries due to their enhanced stability and safety. Among these, the garnet-type Li₇La₃Zr₂O₁₂ (LLZO) solid electrolyte has attracted significant research interest due to its wide electrochemical stability window and good air stability. However, the ionic conductivity of LLZO is lower due to its high sintering temperature and unstable phase structure. In this study, Li_6.4+xFe_0.2La₃Zr_2−xBi_xO₁₂ (x = 0, 0.05, 0.1, 0.15) solid electrolytes were synthesized using a conventional solid-state reaction method by co-doping LLZO with Fe³⁺ and Bi³⁺ ions. Compared with pure LLZO, doping with Fe³⁺ effectively stabilizes the cubic phase, thereby enhancing the ionic conductivity. Moreover, Bi³⁺ doping significantly lowers the sintering temperature of the electrolyte, which in turn reduces energy consumption during the processing. The co-doping of Fe³⁺ and Bi³⁺ not only improves the density of the LLZO electrolyte, achieving a relative density of up to 95%, but also increases the ionic conductivity, with a maximum value of 7.57 × 10⁻⁴ S·cm⁻¹ observed at the optimal composition (Li_6.4+xFe_0.2La₃Zr_2-xBi_xO₁₂, x = 0.1). Full article

(This article belongs to the Collection Green Energy and Environmental Materials)

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12 pages, 739 KiB

Open AccessArticle

Influence of Electron Transfer Mediators in the Pd(II)-Catalyzed Oxidative Carbonylation of Aniline

by Andrea Vavasori, Lucio Ronchin, Luca Pietrobon and Sara Bravo

Molecules 2025, 30(9), 2027; https://doi.org/10.3390/molecules30092027 (registering DOI) - 2 May 2025

Abstract

Currently, the most promising alternative to the use of the phosgenation reaction, for large-scale production of isocyanates, ureas, and carbamates, appears to be the Pd-catalyzed oxidative carbonylation of arylamines. During the reaction, the Pd(II) catalytic species are reduced to Pd(0) and the addition [...] Read more.

Currently, the most promising alternative to the use of the phosgenation reaction, for large-scale production of isocyanates, ureas, and carbamates, appears to be the Pd-catalyzed oxidative carbonylation of arylamines. During the reaction, the Pd(II) catalytic species are reduced to Pd(0) and the addition of sacrificial oxidizing agents is usually necessary to restart the catalytic cycle. Among these oxidizing agents, molecular oxygen is undoubtedly the more appealing, from an economical and green point of view, but it is not so efficient, whereas several metal salts (named cocatalysts) can be used, able to form redox couples with Pd(0) or to act as electron transfer mediators with oxygen itself. Testing several Pd(II) complexes, metal cocatalysts, and promoters, we have found that the [PdCl₂(dppf)]/FeCl₃/LiBr = 1/1200/200 (mol/mol) system efficiently catalyzes the carbonylation of aniline to form 1,3–diphenylurea selectively (100%) with a TOF of ca. 1177 h⁻¹. On the other hand, the addition of oxygen to such a system strongly increases the aniline conversion (0.3 MPa of O₂ increases the TOF at ca. 3930 h⁻¹), but it moves the selectivity towards the phenyl isocyanate (65%, mol/mol). Full article

(This article belongs to the Section Applied Chemistry)

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14 pages, 7097 KiB

Open AccessArticle

Echinacoside Ameliorates UVB-Induced Skin Damage Through Selective Inhibition of the Cutaneous TRPV3 Channel

by Shilun Mo, Xinying Yue, Yaxuan Qu, Guoji Zhang, Liqin Wang and Xiaoying Sun

Molecules 2025, 30(9), 2026; https://doi.org/10.3390/molecules30092026 (registering DOI) - 2 May 2025

Abstract

Excessive exposure to ultraviolet B (UVB) radiation can lead to skin damage, such as erythema and swelling. Echinacoside is a key effective ingredient of medicinal plant Cistanche deserticola commonly used for therapies and treatments for anti-aging and irradiation-related skin diseases. However, the molecular [...] Read more.

Excessive exposure to ultraviolet B (UVB) radiation can lead to skin damage, such as erythema and swelling. Echinacoside is a key effective ingredient of medicinal plant Cistanche deserticola commonly used for therapies and treatments for anti-aging and irradiation-related skin diseases. However, the molecular mechanism underlying the action of echinacoside remains unclear. Here, we report that echinacoside ameliorates UVB-induced skin damage by directly acting on the Ca²⁺-permeable and thermosensitive transient receptor potential vanilloid 3 (TRPV3) channel. Topical application of echinacoside efficaciously suppresses skin lesions induced by UVB radiation in wild-type mice but has no additional benefit in Trpv3 knockout mice. In whole-cell patch clamp recordings, echinacoside selectively inhibits TRPV3 channel currents induced by 2-aminoethoxydiphenyl borate in a concentration-dependent manner with an IC₅₀ value of 21.94 ± 1.28 μM. The single-channel patch clamp results show that echinacoside significantly reduces the open probability and open frequency without significantly altering TRPV3 channel unitary conductance. Molecular docking and site-specific mutagenesis indicate that residue T636 on the p-loop and residue T665 on the S6 segment of TRPV3 are critical for echinacoside binding to TRPV3. Taken together, our findings provide a molecular basis for further studies as use of natural echinacoside in irradiation-related skin care therapy, thus establishing a significant role of the TRPV3 channel in acute skin injury. Full article

(This article belongs to the Special Issue Isolation, Identification and Application of Biologically Active Natural Products—Second Edition)

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20 pages, 8050 KiB

Open AccessArticle

Investigating Natural Product Inhibitors of IKKα: Insights from Integrative In Silico and Experimental Validation

by Muhammad Yasir, Jinyoung Park, Eun-Taek Han, Jin-Hee Han, Won Sun Park, Jongseon Choe and Wanjoo Chun

Molecules 2025, 30(9), 2025; https://doi.org/10.3390/molecules30092025 (registering DOI) - 2 May 2025

Abstract

Nuclear factor-κB (NF-κB) signaling plays a pivotal role in regulating immune responses and is strongly implicated in cancer progression and inflammation-related diseases. The inhibitory κB kinases (IKKs), particularly IKKα, are central to modulating NF-κB activity, with distinct roles in the canonical and non-canonical [...] Read more.

Nuclear factor-κB (NF-κB) signaling plays a pivotal role in regulating immune responses and is strongly implicated in cancer progression and inflammation-related diseases. The inhibitory κB kinases (IKKs), particularly IKKα, are central to modulating NF-κB activity, with distinct roles in the canonical and non-canonical signaling pathways. This study investigates the potential of selectively targeting IKKα to develop novel therapeutic strategies. A receptor–ligand interaction pharmacophore model was generated based on the co-crystallized structure of IKKα, incorporating six key features, two hydrogen bond acceptors, two hydrogen bond donors, one hydrophobic region, and one hydrophobic aromatic region. This model was used to virtually screen a diverse natural compound library of 5540 molecules, yielding 82 candidates that matched the essential pharmacophore features. Molecular docking and molecular dynamics simulations were subsequently employed to evaluate binding conformations, stability, and dynamic behavior of the top hits. The end-state free energy calculations (gmx_MMPBSA) further validated the interaction strength and stability of selected compounds. To experimentally confirm their inhibitory potential, key compounds were tested in LPS-stimulated RAW 264.7 cells, where they significantly reduced IκBα phosphorylation. These findings validate the integrative computational-experimental approach and identify promising natural compounds as selective IKKα inhibitors for further therapeutic development in cancer and inflammatory diseases. Full article

(This article belongs to the Special Issue Role of Natural Products in Inflammation)

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13 pages, 4571 KiB

Open AccessArticle

Evaluation of PAMAM Dendrimer-Stabilized Gold Nanoparticles: Two-Stage Procedure Synthesis and Toxicity Assessment in MCF-7 Breast Cancer Cells

by Agnieszka Maria Kołodziejczyk, Magdalena Grala and Łukasz Kołodziejczyk

Molecules 2025, 30(9), 2024; https://doi.org/10.3390/molecules30092024 (registering DOI) - 2 May 2025

Abstract

Gold nanoparticles stabilized with polyamidoamine dendrimers are one of the potential candidates for use as a contrast agent in computed tomography and a drug delivery agent. This work demonstrates a rapid, two-step synthesis of such complexes, which are size-stable for up to 18 [...] Read more.

Gold nanoparticles stabilized with polyamidoamine dendrimers are one of the potential candidates for use as a contrast agent in computed tomography and a drug delivery agent. This work demonstrates a rapid, two-step synthesis of such complexes, which are size-stable for up to 18 months. The first step of the synthesis involves a short sonication of gold (III) chloride hydrate with polyamidoamine dendrimers of the fourth generation, while the second step uses microwaves to reduce gold (III) chloride hydrate with sodium citrate. The developed synthesis method enables rapid production of spherical and monodisperse gold nanoparticles stabilized with polyamidoamine dendrimers. Physicochemical characterization of the gold nanoparticle-polyamidoamine dendrimers complexes was performed using ultraviolet-visible spectroscopy, dynamic light scattering technique, infrared spectroscopy, atomic force microscopy, and transmission electron microscopy. The toxicity of synthesized complexes on the breast cancer MCF-7 cell line has been studied using the tetrazolium salt reduction test. The produced gold nanoparticles revealed lower toxicity levels on the MCF-7 cell line after 18 months from synthesis compared with newly synthesized colloids. Synthesized gold nanoparticles stabilized with dendrimers and commercially available gold nanoparticles stabilized with sodium citrate show similar toxicity levels on breast cancer cells. Full article

(This article belongs to the Special Issue Nanomaterials for Advanced Biomedical Applications, 2nd Edition)

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15 pages, 1754 KiB

Open AccessArticle

Capillary Electrophoresis Electrospray Ionization Mass Spectrometry Reveals Metabolic Perturbations During Nematode Infection in Drosophila melanogaster

by Yayra T. Tuani, Navid J. Ayon, Rosemary M. Onjiko, Sam B. Choi, Shruti Yadav, Ioannis Eleftherianos and Peter Nemes

Molecules 2025, 30(9), 2023; https://doi.org/10.3390/molecules30092023 - 1 May 2025

Abstract

Drosophila melanogaster is broadly used to model host–pathogen interactions. Entomopathogenic nematodes are excellent research tools for dissecting the molecular and functional basis of parasitism and the host’s anti-parasitic response. In this work, we used discovery metabolomics to explore the differences in the metabolome [...] Read more.

Drosophila melanogaster is broadly used to model host–pathogen interactions. Entomopathogenic nematodes are excellent research tools for dissecting the molecular and functional basis of parasitism and the host’s anti-parasitic response. In this work, we used discovery metabolomics to explore the differences in the metabolome composition of wild type D. melanogaster larvae that were infected with symbiotic nematodes (Steinernema carpocapsae carrying Xenorhabdus nematophila mutualistic bacteria) or axenic nematodes (S. carpocapsae lacking their bacterial partners). Benefiting from their high separation power, sensitivity, and compatibility with low amounts of the starting metabolome, we leveraged microanalytical capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS) to profile the small (<500 Da) polar portion of the metabolome among these experimental treatments. We detected and quantified 122 different small molecules, of which 50 were identified with high confidence. Supervised multivariate analysis revealed that the infection was paralleled with changes in amino acid biosynthesis (arginine, phenylalanine, tryptophan, and tyrosine), metabolism (alanine, arginine, aspartate, glutamate, glycine, proline, serine, and threonine), and classical signalling (aspartate, γ-aminobutyrate, glutamate, and pyridoxine). This study demonstrates the ability of high-sensitivity CE-ESI-MS to uncover metabolic perturbations during infection. The results from the metadata may facilitate the design of targeted studies to explore small biomolecules and their functions during host–pathogen interaction. Full article

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13 pages, 2408 KiB

Open AccessFeature PaperArticle

Enhancing Antioxidant and Anti-Inflammatory Activities of Garlic by Puffing

by Hye-Jung Yang, Jae-Sung Shin, Seon-Min Oh, Ji-Eun Bae, Sang-Jin Ye, Hyun-Wook Choi and Moo-Yeol Baik

Molecules 2025, 30(9), 2022; https://doi.org/10.3390/molecules30092022 - 1 May 2025

Abstract

Garlic (Allium sativum L.) is well known for its numerous health benefits; however, its strong flavor and aroma may limit its consumption due to gastrointestinal discomfort. This study aimed to evaluate puffing as a novel garlic processing method and compare the properties [...] Read more.

Garlic (Allium sativum L.) is well known for its numerous health benefits; however, its strong flavor and aroma may limit its consumption due to gastrointestinal discomfort. This study aimed to evaluate puffing as a novel garlic processing method and compare the properties of puffed garlic with those of raw and black garlic (BG). Puffing was applied at different pressures after adjusting moisture content, resulting in significant physicochemical changes, including increased browning and the development of a porous, crunchy texture. In contrast, BG exhibited a black coloration and a gelatinous texture. Puffing resulted in a marked improvement in extraction yield (except at 196 kPa) and an increase in Maillard reaction products (MRPs), which correlated with the intensity of browning. Although the total phenolic content (TPC) and total flavonoid content (TFC) increased three-fold and eight-fold, respectively, compared to raw garlic, the antioxidant activities determined by DPPH and ABTS radical scavenging activities increased by 22-fold and 61-fold, respectively, compared to raw garlic. All garlic samples demonstrated anti-inflammatory activity, with puffing pressure significantly influencing the suppression of IL-6 production. While BG is widely recognized for its enhanced health-promoting properties, puffed garlic exhibited comparable antioxidant and anti-inflammatory benefits in a shorter time frame and with a better retention of garlic’s original flavor. These findings highlight puffing as an efficient and promising alternative to traditional garlic processing, enhancing functionality while reducing sensory drawbacks. Full article

(This article belongs to the Special Issue Extraction and Analysis of Natural Products in Food—2nd Edition)

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14 pages, 2486 KiB

Open AccessArticle

Modification and Application of Natural Clinoptilolite and Mordenite from Almaty Region for Drinking Water Purification

by Mudasir Zahid, Yerlan Doszhanov, Karina Saurykova, Noorahmad Ahmadi, Didar Bolatova, Meruyert Kurmanbayeva, Akbope Aydarbek, Rahmuddin Ihsas, Makpal Seitzhanova, Dana Akhmetzhanova, Almagul Kerimkulova and Ospan Doszhanov

Molecules 2025, 30(9), 2021; https://doi.org/10.3390/molecules30092021 - 30 Apr 2025

Abstract

In this paper, the modification of natural clinoptilolite and mordenite zeolites from Almaty using acid treatment is addressed for the purposes of improving adsorption performance and for drinking water purification. Structural chemical transformation was characterized by the use of X-ray diffraction (XRD), Fourier-transform [...] Read more.

In this paper, the modification of natural clinoptilolite and mordenite zeolites from Almaty using acid treatment is addressed for the purposes of improving adsorption performance and for drinking water purification. Structural chemical transformation was characterized by the use of X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Scanning electron microscope (SEM) techniques. Acid treatment led to a partial dealumination that was responsible for an increase in the number of surface defects and micropores, improvement in ion exchange capacity, and selectivity toward heavy metals. Additionally, modifications greatly enhance the uptake capacities of Pb²⁺, Cd²⁺, and As³⁺. The clinoptilolite post-modification removal efficiencies reached 94%, 86%, and 84%, respectively, while mordenite zeolites achieved 95%, 90%, and 87% removal efficiencies, respectively. The enhancement of performance was related to the increase in surface area and active sites for ion exchange, verified from analysis of the Brunauer-Emmett-Teller (BET) surface area. The use of different Bhatt and Kothari methods has revealed that adsorption processes followed Langmuir isotherm models for Pb²⁺ and Cd²⁺, whereas As³⁺ adsorption was better described by the Freundlich isotherm model. However, second-order kinetics indicate that chemisorption was the dominant mechanism. Such evidence indicates spontaneity and an endothermic process, as shown from thermodynamic studies. Results showed that modified zeolites indeed had a high degree of reusability, with over 80% of the adsorption capacity retained even after five cycles. Acid-modified zeolites can provide cheaper, greener methods of purification, generating only negligible secondary waste when compared to conventional methods of water purification, for example, activated carbon and membrane filtration. Results from this study proved that modified clinoptilolite and mordenite zeolites have the potential for sustainable heavy metal treatment in drinking water purification systems. Full article

(This article belongs to the Special Issue Zeolites and Mesoporous Materials: Properties and Applications, 2nd Edition)

16 pages, 1390 KiB

Open AccessArticle

¹H-NMR Guided Isolation of Bioactive Compounds from Species of the Genus Piper

by Celso R. Oliveira, Megan J. Burroughs, Lora A. Richards, Lee A. Dyer, Federico Urbano-Muñoz, Camryn Lee, Megan Warner, Craig D. Dodson, Ian S. Wallace and Christopher S. Jeffrey

Molecules 2025, 30(9), 2020; https://doi.org/10.3390/molecules30092020 - 30 Apr 2025

Abstract

The discovery of bioactive natural products is often challenged by the complexity of isolating and characterizing active compounds within diverse mixtures. Previously, we introduced a ¹H NMR-based weighted gene correlation network analysis (WGCNA) approach to identify spectral features linked to growth inhibitory [...] Read more.

The discovery of bioactive natural products is often challenged by the complexity of isolating and characterizing active compounds within diverse mixtures. Previously, we introduced a ¹H NMR-based weighted gene correlation network analysis (WGCNA) approach to identify spectral features linked to growth inhibitory activity of Piper (Piperaceae) leaf extracts against model plant, fungal, and bacterial organisms. This method enabled us to prioritize specific spectral features linked to bioactivity, offering a targeted approach to natural product discovery. In this study, we validate the predictive capacity of the WGCNA by isolating the compounds responsible for the bioactivity-associated resonances and confirming their antifungal efficacy. Using growth inhibition assays, we verified that the isolated compounds, including three novel antifungal agents, exhibited significant bioactivity. Notably, one of these compounds contains a rare imidazolium heterocyclic motif, marking a new structural class in Piper. These findings substantiate the ¹H NMR-based WGCNA as a reliable tool for identifying structural types associated with biological activity, streamlining the process of discovering bioactive natural products in complex extracts. Full article

(This article belongs to the Special Issue The 30th Anniversary of Molecules—Recent Advances in Natural Products Chemistry)

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20 pages, 2143 KiB

Open AccessArticle

Alpha and Omega Classification of β-Lactamase/Transpeptidase-like Superfamily Proteins Based on the Comparison of Their Structural Catalytic Cores

by Alexander I. Denesyuk, Konstantin Denessiouk, Mark S. Johnson and Vladimir N. Uversky

Molecules 2025, 30(9), 2019; https://doi.org/10.3390/molecules30092019 - 30 Apr 2025

Abstract

β-Lactamase/transpeptidase-like superfamily proteins are serine proteases that use the Ser–Lys catalytic dyad to carry out their biological functions. Here, we investigate the three known families of β-lactamase/transpeptidase-like superfamily proteins, β-lactamase/D-Ala carboxypeptidase, glutaminase, and Dac-like, and describe the structural catalytic cores that govern the [...] Read more.

β-Lactamase/transpeptidase-like superfamily proteins are serine proteases that use the Ser–Lys catalytic dyad to carry out their biological functions. Here, we investigate the three known families of β-lactamase/transpeptidase-like superfamily proteins, β-lactamase/D-Ala carboxypeptidase, glutaminase, and Dac-like, and describe the structural catalytic cores that govern the catalytic residues in these proteins. We show that the structural catalytic core of these proteins is a combination of three zones, the mutual three-dimensional arrangement of which correspondingly determines their belonging to one of seven and twenty-four established groups and subgroups. Full article

(This article belongs to the Special Issue Exclusive Feature Papers on Molecular Structure, 2nd Edition)

34 pages, 2273 KiB

Open AccessArticle

Storage Time in Bottle: Influence on Physicochemical and Phytochemical Characteristics of Wine Spirits Aged Using Traditional and Alternative Technologies

by Sheila C. Oliveira-Alves, Tiago A. Fernandes, Sílvia Lourenço, Joana Granja-Soares, Andreia B. Silva, Maria Rosário Bronze, Sofia Catarino and Sara Canas

Molecules 2025, 30(9), 2018; https://doi.org/10.3390/molecules30092018 - 30 Apr 2025

Abstract

Few studies have investigated the influence on physicochemical and phytochemical compositions during storage in the bottle of wine spirits (WSs) aged using alternative ageing technology (AAT) compared to traditional ageing technology (TAT). The aim of this study was to evaluate the effect of [...] Read more.

Few studies have investigated the influence on physicochemical and phytochemical compositions during storage in the bottle of wine spirits (WSs) aged using alternative ageing technology (AAT) compared to traditional ageing technology (TAT). The aim of this study was to evaluate the effect of the bottle storage over one and four years on the evolution of chromatic characteristics (CIELab method) and physicochemical characteristics (alcoholic strength, acidity, and total dry extract), total phenolic index (TPI), low molecular weight compound contents (HPLC-DAD technique), in vitro antioxidant activities (DPPH, FRAP, and ABTS assays), and phenolic characterisation (HPLC-DAD-ESI-MS/MS technique) of WSs aged with chestnut wood using TAT (barrels, B) and AAT (micro-oxygenation levels (MOX): O15, O30, and O60; and control (N)). The results showed that after four years of storage in the bottle, the O60 modality resulted in smaller changes in physicochemical characteristics, higher preservation of phenolic content, and greater evolution of chromatic characteristics, ensuring its overall quality compared to other modalities. Antioxidant activity decreased similarly in both technologies, such as phenolic acid content, in particular, gallic acid content. According to the findings of this study, alternative ageing technology might be the best alternative for wine spirit quality and ageing process sustainability. Full article

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48 pages, 3338 KiB

Open AccessReview

A Comprehensive Review of the Phenolic Compounds in Dracocephalum Genus (Lamiaceae) Related to Traditional Uses of the Species and Their Biological Activities

by Izabela Weremczuk-Jeżyna and Izabela Grzegorczyk-Karolak

Molecules 2025, 30(9), 2017; https://doi.org/10.3390/molecules30092017 - 30 Apr 2025

Abstract

The genus Dracocephalum (family Lamiaceae) comprises approximately 70 species, many of which have been traditionally used in various ethnomedical systems. The plants exhibit a broad distribution across steppe, semi-deserts, deserts, and alpine zones of temperate Eurasia, with isolated endemic species occurring in North [...] Read more.

The genus Dracocephalum (family Lamiaceae) comprises approximately 70 species, many of which have been traditionally used in various ethnomedical systems. The plants exhibit a broad distribution across steppe, semi-deserts, deserts, and alpine zones of temperate Eurasia, with isolated endemic species occurring in North America and North Africa. The traditional medicinal uses of the Dracocephalum species encompass the treatment of respiratory diseases, colds and fever, gastrointestinal disorders, liver and gallbladder ailments, musculoskeletal conditions, cardiovascular diseases, diabetes, gynecological and urological disorders, as well as ailments of the ears, throat, mouth, and eyes, as well as various dermatological conditions. The plants are rich sources of polyphenolic compounds, including flavonoids and phenolic acids, which contribute to their diverse pharmacological activities. The flavonoid profile of the Dracocephalum species is dominated by luteolin and apigenin derivatives, supplemented by mono-, di-, tri-, tetra-, and pentamethoxylated flavones. The predominant phenolic acids are chlorogenic acid, coumaric acid, rosmarinic acid, and their derivatives. Other phenolic compounds have also been identified in the genus: anthocyanins, lignans, phenylethanoids, phenylacetamide glycosides, flavonoid alkaloids, gingerols, coumarins, furanocoumarins, and cyanogenic glucosides. Despite growing scientific interest in this genus, a comprehensive review of its polyphenolic constituents, their structures, and associated biological activities remains lacking. To bridge this gap, this review presents an analysis of the polyphenolic profile of the Dracocephalum species, their ethnomedicinal uses, and the latest findings on their biological potential. Full article

(This article belongs to the Special Issue Biological Activity of Plant Extracts)

17 pages, 645 KiB

Open AccessArticle

Synthesis and Biological Screening of Structurally Modified Phaeosphaeride Analogues

by Konstantinos Rantzios, Oraia-Eirini Chatzimentor, George Leonidis, Jorgo Giuliani, Ioanna Sigala and Vasiliki Sarli

Molecules 2025, 30(9), 2016; https://doi.org/10.3390/molecules30092016 - 30 Apr 2025

Abstract

Phaeosphaeride A and its analogues have been extensively explored for their potential pharmacological applications, particularly in the development of anticancer agents. In this study, the synthesis of structurally modified phaeosphaeride analogues is reported. The structures of the synthesized analogues bearing the tetrahydro- and [...] Read more.

Phaeosphaeride A and its analogues have been extensively explored for their potential pharmacological applications, particularly in the development of anticancer agents. In this study, the synthesis of structurally modified phaeosphaeride analogues is reported. The structures of the synthesized analogues bearing the tetrahydro- and hexahydro-2H-furo[3,2-b]pyran-2-one and hexahydropyrano[3,2-b]pyrrol-2(1H)-one moieties were assessed and the new compounds were evaluated for their antiproliferative activity against two cancer cell lines. Despite successful synthesis and structural modification, the majority of the phaeosphaeride analogues exhibited limited bioactivity. Structure-activity relationship studies suggested that specific modifications did not enhance anticancer potency. The hydroxy groups and the alkyl moiety in cyclic or non-cyclic phaeosphaeride analogues contribute to the activity, as shown by the activity of compounds 24 and 25. The presence of double bonds and oxygen or nitrogen heteroatoms in furopyranones or pyranopyrrolones 9, 28, 29 and 33a, does not significantly impact cytotoxic activity. These findings highlight the challenges in optimizing phaeosphaerides for anticancer applications and provide insights into future structural modifications to improve their therapeutic potential. Moreover, our studies open a synthetic route for the development of new phaeosphaeride analogues. Full article

(This article belongs to the Section Medicinal Chemistry)

17 pages, 3416 KiB

Open AccessArticle

Influence of Enzymatic Acylation on the Stability and Antioxidant Properties of Cyanidin-3-O-Glucoside in Both Aqueous and Lipid Systems

by Ziwei Ye, Mingyun Liu, Jingmei Lyu, Han Rong and Lujing Gan

Molecules 2025, 30(9), 2015; https://doi.org/10.3390/molecules30092015 - 30 Apr 2025

Abstract

Cyanidin-3-O-glucoside (C3G) was used as a substrate for enzymatic acylation, and different compounds (methyl n-octanoate and methyl salicylate) were selected as acyl donors. Structural analysis (UV–Vis, FTIR, and HPLC) revealed the successful integration of methyl ester compounds into the structural [...] Read more.

Cyanidin-3-O-glucoside (C3G) was used as a substrate for enzymatic acylation, and different compounds (methyl n-octanoate and methyl salicylate) were selected as acyl donors. Structural analysis (UV–Vis, FTIR, and HPLC) revealed the successful integration of methyl ester compounds into the structural units of C3G. The thermostability and photostability of acylated C3Gs, particularly those with methyl salicylate as the acyl donor, exhibited significant improvements. The molecular geometries of the different anthocyanins were optimized using computational chemistry, and energy level calculations were performed by using Density Functional Theory (DFT) to identify the antioxidant active site. Then, the antioxidant properties of C3G and acylated C3Gs (O-C3G and S-C3G) were studied in both aqueous and lipid systems. In aqueous systems, acylated C3Gs exhibited higher antioxidant properties than C3G in DPPH radical scavenging and hydroxyl radical scavenging assays, with cyanidin-3-O-glucoside salicyl acyl product (S-C3G) demonstrating the highest activity. However, the antioxidant properties varied in lipid systems. In lipid systems, acylated C3Gs displayed better antioxidant properties than C3G in POV and TBARS assays, with cyanidin-3-O-glucoside n-octanoate acid acyl product (O-C3G) showing better antioxidant properties compared to that in aqueous systems. Full article

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14 pages, 651 KiB

Open AccessArticle

Synthesis of 1,4-Benzodiazepines via Intramolecular C–N Bond Coupling and Ring Opening of Azetidines

by Xin-Ming Xu, Sen Chen, Shao-Lei Duan, Xiang-Min Wang, Qian Liu and Kai Sun

Molecules 2025, 30(9), 2014; https://doi.org/10.3390/molecules30092014 - 30 Apr 2025

Abstract

A facile and efficient synthesis of functionalized 1,4-benzodiazepine derivatives under mild conditions was developed. The CuI/N,N-dimethylglycine-catalyzed intramolecular cross-coupling reaction of 1-(2-bromobenzyl)azetidine-2-carboxamides proceeded smoothly under mild conditions to provide 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones. The resulting azetidine-fused 1,4-benzodiazepine compounds underwent [...] Read more.

A facile and efficient synthesis of functionalized 1,4-benzodiazepine derivatives under mild conditions was developed. The CuI/N,N-dimethylglycine-catalyzed intramolecular cross-coupling reaction of 1-(2-bromobenzyl)azetidine-2-carboxamides proceeded smoothly under mild conditions to provide 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones. The resulting azetidine-fused 1,4-benzodiazepine compounds underwent consecutive N-methylation with methyl triflate and the opening of the four-membered heterocyclic ring by NaN₃, KCN and PhSNa to produce diverse 1,4-benzodiazepine derivatives in good to excellent yields. Upon treatment with methyl chloroformate, on the other hand, the 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones were straightforwardly converted into 2-chloroethyl-substituted 1,4-benzodiazepine derivatives. Full article

(This article belongs to the Special Issue Synthesis, Modification and Application of Heterocyclic Compounds)

18 pages, 642 KiB

Open AccessReview

Comparative Analysis of Lespedeza Species: Traditional Uses and Biological Activity of the Fabaceae Family

by Roxana-Delia Chitiala, Ionut Iulian Lungu, George-Alexandru Marin, Andreea-Maria Mitran, Ioana-Cezara Caba, Andreea Lungu, Silvia Robu, Cornelia Mircea, Alina Stefanache, Monica Hancianu and Oana Cioanca

Molecules 2025, 30(9), 2013; https://doi.org/10.3390/molecules30092013 - 30 Apr 2025

Abstract

With around 40 species spread throughout temperate and subtropical environments, mostly in East Asia and North America, the genus Lespedeza (Fabaceae) includes a variety of species that have been used in traditional folk medicine for centuries. Particularly in antioxidant, anti-inflammatory, anticancer, [...] Read more.

With around 40 species spread throughout temperate and subtropical environments, mostly in East Asia and North America, the genus Lespedeza (Fabaceae) includes a variety of species that have been used in traditional folk medicine for centuries. Particularly in antioxidant, anti-inflammatory, anticancer, and antidiabetic applications, Lespedeza species show notable pharmacological promise, due in large part to their high polyphenolic content. With a 2,2-diphenyl-1-picrylhydrazyl (DPPH) IC50 of 20–25 µg/mL and a ferric ion reducing antioxidant power (FRAP) value of 819.5 µmol Fe²⁺/g, L. cuneata demonstrated the highest antioxidant activity among the three Lespedeza species. The rich polyphenolic profile includes quercetin, catechin, rutin, and special substances like lespeflorin B/C and lespecunioside A/B, which explain its efficacy. Its broad-spectrum action across DPPH, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) tests points to its importance for neuroprotective and anti-aging uses. Anti-inflammatory studies support its capacity to downregulate tumor necrosis factor (TNF-α) and interleukin 6 (IL-6) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) suppression. L. bicolor has shown excellent promise, owing to its high total flavonoid content (109.2 mg QE/g) and presence of bioactives including kaempferol-3-O-rutinoside and xanthoangelol, albeit displaying somewhat lower antioxidant capacity (FRAP: 912.3 µmol Fe²⁺/g). In macrophage models it showed clear anti-inflammatory action. Its capacity to prevent advanced glycation end products’ (AGEs) generation ties it to possible antidiabetic and antiaging effects. Although it showed the worst antioxidant profile (IC50: 40–60 µg/mL; FRAP: 743.2 µmol Fe²⁺/g), L. capitata nonetheless had useful components like quercetin, chlorogenic acid, and lespedecapitoside (syn. isoorientin). Though little researched, they have modest antioxidant, nephroprotective, and anti-inflammatory action. Full article

(This article belongs to the Special Issue Biological Activities of Traditional Medicinal Plants, 2nd Edition)

52 pages, 1634 KiB

Open AccessReview

Early-Stage Pancreatic Cancer Diagnosis: Serum Biomarkers and the Potential for Aptamer-Based Biosensors

by Weisi He, Jingyu Cui, Xue-Yan Wang, Ryan H. P. Siu and Julian A. Tanner

Molecules 2025, 30(9), 2012; https://doi.org/10.3390/molecules30092012 - 30 Apr 2025

Abstract

Pancreatic cancer has a high mortality rate, and both the incidence and mortality are continuing to increase in many countries globally. The poor prognosis of pancreatic cancer is in part due to the challenges in early diagnosis. Improving early-stage pancreatic cancer diagnosis would [...] Read more.

Pancreatic cancer has a high mortality rate, and both the incidence and mortality are continuing to increase in many countries globally. The poor prognosis of pancreatic cancer is in part due to the challenges in early diagnosis. Improving early-stage pancreatic cancer diagnosis would improve survival outcomes. Aptamer-based biosensors provide an alternative technological approach for the analysis of serum biomarkers with several potential advantages. This review summarizes the major pancreatic cancer serum biomarkers, as well as discusses recent progress in biomarker exploration and aptasensor development. Here, we review both established and novel serum biomarkers identified recently, emphasizing their potential for early-stage pancreatic cancer diagnosis. We also propose strategies for further expanding multiplex biomarker panels beyond the established CA19-9 biomarker to enhance diagnostic performance. We discuss technological advancements in aptamer-based sensors for pancreatic cancer-related biomarkers over the last decade. Optical and electrochemical sensors are highlighted as two primary modalities in aptasensor design, each offering unique advantages. Finally, we propose steps towards clinical application using aptamer-based sensors with multiplexed biomarker detection for improved pancreatic cancer diagnostics. Full article

(This article belongs to the Special Issue The 30th Anniversary of Molecules—Recent Advances in Chemical Biology)

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