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1.
Planta Med ; 90(7-08): 631-640, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843801

ABSTRACT

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.


Subject(s)
Garcinia , Magnetic Resonance Spectroscopy , Garcinia/chemistry , Molecular Structure , Fruit/chemistry , Benzophenones/chemistry , Benzophenones/isolation & purification , Benzophenones/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Phytochemicals/isolation & purification , Phytochemicals/chemistry , Phytochemicals/pharmacology , Phloroglucinol/chemistry , Phloroglucinol/isolation & purification , Humans
2.
Langmuir ; 40(20): 10648-10662, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38712915

ABSTRACT

This study presents new insights into the potential role of polyelectrolyte interfaces in regulating low friction and interstitial fluid pressurization of cartilage. Polymer brushes composed of hydrophilic 3-sulfopropyl methacrylate potassium salt (SPMK) tethered to a PEEK substrate (SPMK-g-PEEK) are a compelling biomimetic solution for interfacing with cartilage, inspired by the natural lubricating biopolyelectrolyte constituents of synovial fluid. These SPMK-g-PEEK surfaces exhibit a hydrated compliant layer approximately 5 µm thick, demonstrating the ability to maintain low friction coefficients (µ ∼ 0.01) across a wide speed range (0.1-200 mm/s) under physiological loads (0.75-1.2 MPa). A novel polyelectrolyte-enhanced tribological rehydration mechanism is elucidated, capable of recovering up to ∼12% cartilage strain and subsequently facilitating cartilage interstitial fluid recovery, under loads ranging from 0.25 to 2.21 MPa. This is attributed to the combined effects of fluid confinement within the contact gap and the enhanced elastohydrodynamic behavior of polymer brushes. Contrary to conventional theories that emphasize interstitial fluid pressurization in regulating cartilage lubrication, this work demonstrates that SPMK-g-PEEK's frictional behavior with cartilage is independent of these factors and provides unabating aqueous lubrication. Polyelectrolyte-enhanced tribological rehydration can occur within a static contact area and operates independently of known mechanisms of cartilage interstitial fluid recovery established for converging or migrating cartilage contacts. These findings challenge existing paradigms, proposing a novel polyelectrolyte-cartilage tribological mechanism not exclusively reliant on interstitial fluid pressurization or cartilage contact geometry. The implications of this research extend to a broader understanding of synovial joint lubrication, offering insights into the development of joint replacement materials that more accurately replicate the natural functionality of cartilage.


Subject(s)
Lubrication , Polymers , Polymers/chemistry , Animals , Polyelectrolytes/chemistry , Polyethylene Glycols/chemistry , Cartilage/chemistry , Cartilage/drug effects , Surface Properties , Benzophenones/chemistry , Cartilage, Articular/chemistry , Cartilage, Articular/physiology , Ketones/chemistry
3.
Environ Sci Pollut Res Int ; 31(21): 31201-31212, 2024 May.
Article in English | MEDLINE | ID: mdl-38625467

ABSTRACT

Benzophenone-4 (BP-4) is one of the UV filters widely used in personal care products (PCPs). BP-4 has been identified as an emergent contaminant detected in influent and effluent of wastewater treatment plants (WWTPs) at high concentrations showing that conventional treatment is unable to remove it, subsequently, the presence of BP-4 in surface water is inevitable. In this study, we focus on the degradation of this compound by chlorine, and we report the efficiency of its removal from water by applying two advanced oxidation processes UV/TiO2 and UV/H2O2 aiming to achieve a superior mineralization result. The study was performed in purified water (pH = 6.5, temperature = 25 °C) with an initial concentration of BP-4 similar to that detected in WWTPs (10 mg/L). The results showed that 76% of BP-4 was degraded after 80 min of reaction with chlorine leading to the formation of one by-product persistent in the solution. The oxidation by UV/TiO2 and UV/H2O2 led to a total removal of BP-4 and their generated by-products after 50 and 10 min of reactions, respectively. The kinetic study showed that BP-4 degradation by UV/H2O2 and UV/TiO2 followed pseudo-first-order reaction kinetics and the apparent rate constants (kapp) were determined to be 0.48 min-1 and 0.08 min-1, respectively. The degradation of BP-4 by chlorine followed first-order reaction kinetics with kapp = 0.02 min-1. The identification of by-product structures was performed using liquid chromatography with electrospray ionization and tandem mass spectrometry (MS/MS. The fragmentation of BP-4 and by-product ions at different collision energies allowed to propose the pathways of degradation and to predict the toxicity using a silico toxicity program which confirmed a higher toxicity of all generated by-products.


Subject(s)
Benzophenones , Halogenation , Oxidation-Reduction , Water Pollutants, Chemical , Kinetics , Benzophenones/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods , Wastewater/chemistry , Titanium/chemistry , Hydrogen Peroxide/chemistry
4.
J Mater Chem B ; 12(19): 4533-4552, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38477504

ABSTRACT

Polyetheretherketone (PEEK), as a high-performance polymer, is widely used for bone defect repair due to its homogeneous modulus of elasticity of human bone, good biocompatibility, excellent chemical stability and projectability. However, the highly hydrophobic surface of PEEK is biologically inert, which makes it difficult for cells and proteins to attach, and is accompanied by the development of infections that ultimately lead to failure of PEEK implants. In order to further enhance the potential of PEEK as an orthopedic implant, researchers have explored modification methods such as surface modification by physical and chemical means and the addition of bioactive substances to PEEK-based materials to enhance the mechanical properties, osteogenic activity and antimicrobial properties of PEEK. However, these current modification methods still have obvious shortcomings in terms of cost, maneuverability, stability and cytotoxicity, which still need to be explored by researchers. This paper reviews some of the modification methods that have been used to improve the performance of PEEK over the last three years in anticipation of the need for researchers to design PEEK orthopedic implants that better meet clinical needs.


Subject(s)
Benzophenones , Biocompatible Materials , Ketones , Polyethylene Glycols , Polymers , Prostheses and Implants , Surface Properties , Polymers/chemistry , Polymers/pharmacology , Benzophenones/chemistry , Ketones/chemistry , Ketones/pharmacology , Humans , Polyethylene Glycols/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals
5.
Z Naturforsch C J Biosci ; 79(3-4): 47-60, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38549398

ABSTRACT

Garcinia mangostana fruits are used traditionally for inflammatory skin conditions, including acne. In this study, an in silico approach was employed to predict the interactions of G. mangostana xanthones and benzophenones with three proteins involved in the pathogenicity of acne, namely the human JNK1, Cutibacterium acnes KAS III and exo-ß-1,4-mannosidase. Molecular docking analysis was performed using Autodock Vina. The highest docking scores and size-independent ligand efficiency values towards JNK1, C. acnes KAS III and exo-ß-1,4-mannosidase were obtained for garcinoxanthone T, gentisein/2,4,6,3',5'-pentahydroxybenzophenone and mangostanaxanthone VI, respectively. To the best of our knowledge, this is the first report of the potential of xanthones and benzophenones to interact with C. acnes KAS III. Molecular dynamics simulations using GROMACS indicated that the JNK1-garcinoxanthone T complex had the highest stability of all ligand-protein complexes, with a high number of hydrogen bonds predicted to form between this ligand and its target. Petra/Osiris/Molinspiration (POM) analysis was also conducted to determine pharmacophore sites and predict the molecular properties of ligands influencing ADMET. All ligands, except for mangostanaxanthone VI, showed good membrane permeability. Garcinoxanthone T, gentisein and 2,4,6,3',5'-pentahydroxybenzophenone were identified as the most promising compounds to explore further, including in experimental studies, for their anti-acne potential.


Subject(s)
Acne Vulgaris , Benzophenones , Garcinia mangostana , Molecular Docking Simulation , Xanthones , Xanthones/chemistry , Xanthones/pharmacology , Benzophenones/chemistry , Benzophenones/pharmacology , Garcinia mangostana/chemistry , Humans , Acne Vulgaris/drug therapy , Acne Vulgaris/microbiology , Molecular Dynamics Simulation , Mitogen-Activated Protein Kinase 8/metabolism , Mitogen-Activated Protein Kinase 8/chemistry , Computer Simulation , Hydrogen Bonding
6.
Article in English | MEDLINE | ID: mdl-38518984

ABSTRACT

Benzophenone chemicals (BPs) have been developed to prevent the adverse effects of UV radiation and they are widely contaminated. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) catalyze the conversion of inactive glucocorticoid to active glucocorticoid, playing critical role in many physiological function. However, the direct effect of BPs on human, pig, rat, and mouse 11ß-HSD1 remains unclear. In this study, we screened the inhibitory strength of 12 BPs on 4 species, and performed the structure-activity relationship (SAR) and in silico docking analysis. The inhibitory potency of BPs was: for human 11ß-HSD1, BP6 (IC50 = 18.76 µM) > BP8 (40.84 µM) > BP (88.89 µM) > other BPs; for pig 11ß-HSD1, BP8 (45.57 µM) > BP6 (59.44 µM) > BP2 (65.12 µM) > BP (135.56 µM) > other BPs; for rat 11ß-HSD1, BP7 (67.17 µM) > BP (68.83 µM) > BP8 (133.04 µM) > other BPs; and for mouse 11ß-HSD1, BP8 (41.41 µM) > BP (50.61 µM) > other BPs. These BP chemicals were mixed/competitive inhibitors of these 11ß-HSD1 enzymes. The 2,2'-dihydroxy substitutions in two benzene rings play a key role in enhancing the effectiveness of inhibiting 11ß-HSD1, possibly via increasing hydrogen bond interactions. Docking analysis shows that these BPs bind to NADPH/glucocorticoid binding sites and forms hydrogen bonds with catalytic residues Ser and/or Tyr. In conclusion, this study demonstrates that BP chemicals can inhibit 11ß-HSD1 from 4 species, and there are subtle species-dependent difference in the inhibitory strength and structural variations of BPs.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 1 , Benzophenones , Molecular Docking Simulation , Animals , Benzophenones/chemistry , Benzophenones/pharmacology , 11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 1/metabolism , 11-beta-Hydroxysteroid Dehydrogenase Type 1/chemistry , Humans , Structure-Activity Relationship , Rats , Mice , Swine , Sunscreening Agents/chemistry , Sunscreening Agents/pharmacology , Sunscreening Agents/toxicity , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Species Specificity , Ultraviolet Rays
7.
Environ Sci Technol ; 58(12): 5472-5482, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38466321

ABSTRACT

The fate of selected UV filters (UVFs) was investigated in two soil aquifer treatment (SAT) systems, one supplemented with a reactive barrier containing clay and vegetable compost and the other as a traditional SAT reference system. We monitored benzophenone-3 (BP-3) and its transformation products (TPs), including benzophenone-1 (BP-1), 4,4'-dihydroxybenzophenone (4DHB), 4-hydroxybenzophenone (4HB), and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB), along with benzophenone-4 (BP-4) and avobenzone (AVO) in all involved compartments (water, aquifer sediments, and biofilm). The reactive barrier, which enhances biochemical activity and biofilm development, improved the removal of all detected UVFs in water samples. Among monitored UVFs, only 4HB, BP-4, and AVO were detected in sediment and biofilm samples. But the overall retained amounts were several orders of magnitude larger than those dissolved. These amounts were quantitatively reproduced with a specifically developed simple analytical model that consists of a mobile compartment and an immobile compartment. Retention and degradation are restricted to the immobile water compartment, where biofilm absorption was simulated with well-known compound-specific Kow values. The fact that the model reproduced observations, including metabolites detected in the biofilm but not in the (mobile) water samples, supports its validity. The results imply that accumulation ensures significant biodegradation even if the degradation rates are very low and suggest that our experimental findings for UVFs and TPs can be extended to other hydrophobic compounds. Biofilms act as accumulators and biodegraders of hydrophobic compounds.


Subject(s)
Soil , Water Pollutants, Chemical , Porosity , Sunscreening Agents/analysis , Benzophenones/chemistry , Water/chemistry , Water Pollutants, Chemical/analysis
8.
Phytochem Anal ; 35(3): 445-468, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38069552

ABSTRACT

INTRODUCTION: The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives. OBJECTIVES: The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages. MATERIAL AND METHODS: In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics. RESULTS: This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 µg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 µg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 µg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids. CONCLUSION: To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.


Subject(s)
Clusia , Clusia/chemistry , Fruit/chemistry , Chromatography, Liquid , Tandem Mass Spectrometry , Benzophenones/analysis , Benzophenones/chemistry , Benzophenones/metabolism , Flowers/chemistry , Plant Leaves/chemistry , Metabolomics/methods , Seeds/chemistry , Sugars/analysis
9.
Molecules ; 28(20)2023 Oct 14.
Article in English | MEDLINE | ID: mdl-37894560

ABSTRACT

BACKGROUND: The chemistry of Costa Rican propolis from Apis mellifera remains underexplored despite its potential applications. This study identified its chemical composition, linking chemotypes to antioxidant potential. METHODS: Proton nuclear magnetic resonance (1H NMR) spectra were obtained for 119 propolis extracts and analyzed using multivariate analyses. In parallel, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay was used to assess antioxidant activity. A generalized linear regression model (GLM) correlated this with its chemical profiles and geographical origin. Chromatographic methods were used to isolate active and inactive compounds, which were identified using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). RESULTS: Principal component analysis (PCA) revealed three chemical profile groups for the 119 propolis extracts, explaining 73% of the total variance with two components. Radical scavenging activity was found to correlate with chemical composition. Isolation yielded n-coniferyl benzoate in type I (EC50 = 190 µg/mL, ORAC = 0.60 µmol TE/µmol) and nemorosone in type II (EC50 = 300 µg/mL, ORAC = 0.7 µmol TE/µmol). Type III was represented in terpene-like components, which exhibited lower antioxidant activity. CONCLUSIONS: This study categorizes Costa Rican propolis into three chemical types and identifies two key components linked to antioxidant activity. Notably, nemorosone, a valuable natural product, was found to be highly concentrated in a particular region of Costa Rica.


Subject(s)
Propolis , Animals , Propolis/chemistry , Antioxidants/chemistry , Costa Rica , Benzophenones/chemistry
10.
Environ Sci Technol ; 57(32): 11704-11717, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37515552

ABSTRACT

Photoinitiators (PIs) are a family of anthropogenic chemicals used in polymerization systems that generate active substances to initiate polymerization reactions under certain radiations. Although polymerization is considered a green method, its wide application in various commercial products, such as UV-curable inks, paints, and varnishes, has led to ubiquitous environmental issues caused by PIs. In this study, we present an overview of the current knowledge on the environmental occurrence, human exposure, and toxicity of PIs and provide suggestions for future research based on numerous available studies. The residual concentrations of PIs in commercial products, such as food packaging materials, are at microgram per gram levels. The migration of PIs from food packaging materials to foodstuffs has been confirmed by more than 100 reports of food contamination caused by PIs. Furthermore, more than 20 PIs have been detected in water, sediment, sewage sludge, and indoor dust collected from Asia, the United States, and Europe. Human internal exposure was also confirmed by the detection of PIs in serum. In addition, PIs were present in human breast milk, indicating that breastfeeding is an exposure pathway for infants. Among the most available studies, benzophenone is the dominant congener detected in the environment and humans. Toxicity studies of PIs reveal multiple toxic end points, such as carcinogenicity and endocrine-disrupting effects. Future investigations should focus on synergistic/antagonistic toxicity effects caused by PIs coexposure and metabolism/transformation pathways of newly identified PIs. Furthermore, future research should aim to develop "greener" PIs with high efficiency, low migration, and low toxicity.


Subject(s)
Dust , Food Packaging , Female , Humans , Asia , Benzophenones/chemistry , Water
11.
Phys Chem Chem Phys ; 25(24): 16520-16526, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37306976

ABSTRACT

Here, we report the detailed mechanisms of benzophenone (BZP) photosensitized thymine damage and repair by Paternò-Büchi (PB) cycloaddition. It was found that the head-to-head and head-to-tail PB cycloadditions lead to the formation of the C-O bonds in the 3(nπ*) state and the 3(ππ*) state, respectively. The conical intersection occurs before the head-to-tail C-O bonding. Then, the C-C bonds are formed via intersystem crossing (ISC). The C-O bonding is the rate-determining step of PB cycloaddition. For the cycloreversion reactions, the ring-opening processes completely occur in the singlet excited states of oxetanes. The head-to-head oxetane goes through a conical intersection before cycloreversion with a little energy barrier of 1.8 kcal mol-1. The head-to-tail oxetane splits without a barrier. Then, the ISC processes take place to restore thymine. Throughout the ring-closing and ring-opening processes, ISC plays an important role. These findings are in good agreement with the available experimental findings. We hope that this comprehensive work can provide a deeper understanding of photosensitive DNA damage and repair.


Subject(s)
Benzophenones , Thymine , Thymine/chemistry , Cycloaddition Reaction , Benzophenones/chemistry
12.
Phytochemistry ; 211: 113701, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37127017

ABSTRACT

Ten undescribed benzophenones, schomburginones A-J, together with 14 known analogs were isolated from the leaves of Garcinia schomburgkiana, an edible plant native to the Indochina region. The structures of the undescribed compounds were elucidated by NMR combined with HRMS spectroscopy, while their absolute configurations were determined using ECD and single-crystal X-ray diffraction analysis. The isolated metabolites represent benzophenone derivatives containing a modified monoterpene unit, including tri- and tetracyclic skeletons, which are rarely found in genus Garcinia. The cytotoxic evaluation on three cancerous cell lines demonstrated that schomburginone G, schomburginone H, and 3-geranyl-2,4,6-trihydroxybenzophenone were active against HeLa cells with IC50 values in the range of 12.2-15.7 µM, respectively, and selective compared to the non-cancerous L929 cells (SI > 3.5). In addition, the three cytotoxic compounds together with clusiacyclol A showed significant NO inhibitory activity in RAW 264.7 macrophage cells over 85% inhibition without obvious cytotoxicity at a final concentration of 100 µM. The promising activities of these compounds in cytotoxic and anti-inflammatory assays make them attractive for further study in the development of anticancer drugs.


Subject(s)
Antineoplastic Agents, Phytogenic , Antineoplastic Agents , Garcinia , Xanthones , Humans , HeLa Cells , Molecular Structure , Garcinia/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Benzophenones/pharmacology , Benzophenones/chemistry , Xanthones/chemistry
13.
J Hazard Mater ; 456: 131617, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37224711

ABSTRACT

To carry out risk assessments of benzophenone-type UV filters (BPs), fast and accurate analytical methods are crucial to determine and monitor levels in the environment. This study presents an LC-MS/MS method that requires minimal sample preparation and yet can identify 10 different BPs in environmental samples such as surface or wastewater resulting in a LOQ range from 2 to 1060 ng/L. The method suitability was tested through environmental monitoring, which showed that, BP-4 is the most abundant derivative found in the surface waters of Germany, India, South Africa and Vietnam. BP-4 levels correlate with the WWTP effluent fraction of the respective river for selected samples in Germany. Peak values of 171 ng/L for 4-hydroxybenzophenone (4-OH-BP), as measured in Vietnamese surface water, already exceed the PNEC value of 80 ng/L, elevating 4-OH-BP to the status of a new pollutant that needs more frequent monitoring. Moreover, this study reveals that during biodegradation of benzophenone in river water, the transformation product 4-OH-BP is formed which contain structural alerts for estrogenic activity. By using yeast-based reporter gene assays, this study provides bio-equivalents of 9 BPs, 4-OH-BP, 2,3,4-tri-OH-BP, 4-cresol and benzoate and complements the existing structure-activities relationships of BPs and their degradation products.


Subject(s)
Receptors, Androgen , Water Pollutants, Chemical , Humans , Chromatography, Liquid/methods , Water , Tandem Mass Spectrometry/methods , Estrogens/analysis , Saccharomyces cerevisiae , Benzophenones/chemistry , Sunscreening Agents/chemistry , Water Pollutants, Chemical/chemistry
14.
Molecules ; 28(10)2023 May 13.
Article in English | MEDLINE | ID: mdl-37241815

ABSTRACT

The emergence of multiresistant bacteria and the shortage of antibacterials in the drug pipeline creates the need to search for novel agents. Evolution drives the optimization of the structure of marine natural products to act as antibacterial agents. Polyketides are a vast and structurally diverse family of compounds that have been isolated from different marine microorganisms. Within the different polyketides, benzophenones, diphenyl ethers, anthraquinones, and xanthones have shown promising antibacterial activity. In this work, a dataset of 246 marine polyketides has been identified. In order to characterize the chemical space occupied by these marine polyketides, molecular descriptors and fingerprints were calculated. Molecular descriptors were analyzed according to the scaffold, and principal component analysis was performed to identify the relationships among the different descriptors. Generally, the identified marine polyketides are unsaturated, water-insoluble compounds. Among the different polyketides, diphenyl ethers tend to be more lipophilic and non-polar than the remaining classes. Molecular fingerprints were used to group the polyketides according to their molecular similarity into clusters. A total of 76 clusters were obtained, with a loose threshold for the Butina clustering algorithm, highlighting the large structural diversity of the marine polyketides. The large structural diversity was also evidenced by the visualization trees map assembled using the tree map (TMAP) unsupervised machine-learning method. The available antibacterial activity data were examined in terms of bacterial strains, and the activity data were used to rank the compounds according to their antibacterial potential. This potential ranking was used to identify the most promising compounds (four compounds) which can inspire the development of new structural analogs with better potency and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.


Subject(s)
Polyketides , Xanthones , Xanthones/chemistry , Benzophenones/chemistry , Anthraquinones , Phenyl Ethers , Anti-Bacterial Agents/chemistry , Polyketides/chemistry
15.
Phytochemistry ; 210: 113674, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37044362

ABSTRACT

Nemorosone is a bicyclic polyprenylated acylphloroglucinol derivative originally isolated from Clusia spp. and it can be obtained through chemical synthesis employing different synthetic strategies. Since its discovery, it has attracted great attention both from a biological and chemical viewpoint. In the present article, we attempted to review various chemical and biological topics around nemorosone, with an emphasis on its antiproliferative activities. For this purpose, relevant data was collected from different scientific databases including Google Scholar, PubMed, Scopus and ISI Web of Knowledge. This natural compound has shown activity against several types of malignancies such as leukemia, human colorectal, pancreatic, and breast cancer because it modulates multiple molecular pathways. Nemorosone has both cytostatic and cytotoxic activity and it also seems to induce apoptosis and ferroptosis. Additionally, it has antimicrobial capabilities against Gram-positive bacteria and parasites belonging to genus Leishmania. Its promising antiproliferative pre-clinical effects deserve further attention for anticancer and anti-parasitic drug development and translation to the clinic.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Humans , Female , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Benzophenones/chemistry , Breast Neoplasms/pathology
16.
Bioorg Chem ; 133: 106389, 2023 04.
Article in English | MEDLINE | ID: mdl-36731298

ABSTRACT

Garcinol is a polyisoprenylated benzophenone isolated from Garcinia. It has been reported to have a variety of intriguing biological effects, including anticancer, anti-inflammatory, and antioxidant capabilities. The purpose of this research is to thoroughly evaluate garcinol and a series of its analogues in terms of synthesis, structural diversity, biosynthesis, and potential for preventing carcinoma cell proliferation. Garcinopicrobenzophenone and eugeniaphenone, which contain a unique cyclobutyl unit at C-5, were initially synthesized using the procedures utilized in the synthesis of garcinol. All the natural analogs of garcinol were produced at completion of the synthesis, and their structures and absolute configurations were clarified. Based on the synthesis, a possible biogenetic synthesis pathway towards cambogin, 13,14-didehydroxyisogarcinol via O-cyclization, and garcinopicrobenzophenone or eugeniaphenone via C-cyclization was proposed. The cytotoxicity of polyisoprenylated benzophenones produced in our group was tested, and the structure-activity relationship was summarized. The mechanism by which garcinol, cambogin, and 21' induce apoptosis was studied. Cambogin and 21' were shown to have a greater capacity to cause apoptosis in pancreatic cancer BXPC3 cells, and the suppression of BXPC3 cells by 21' might be attributed to the target of STAT3 signaling. Garcinol could cause pyroptosis and apoptosis in pancreatic cancer cells at the same time, which was the first time that garcinol was identified as a possible chemotherapeutic agent that could significantly promote pyroptosis in cancer cells.


Subject(s)
Antineoplastic Agents , Benzophenones , Pancreatic Neoplasms , Humans , Antineoplastic Agents/pharmacology , Apoptosis , Benzophenones/chemistry , Benzophenones/pharmacology , Pancreatic Neoplasms/metabolism , Signal Transduction , Terpenes/pharmacology
17.
Molecules ; 28(3)2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36770896

ABSTRACT

The ubiquitous presence of emerging contaminants in the environment is an issue of great concern. Notably, for some of them, no established regulation exists. Benzophenones are listed as emerging contaminants, which have been identified in the environment as well as in human fluids, such as urine, placenta, and breast milk. Their accumulation and stability in the environment, combined with the revealed adverse effects on ecosystems including endocrine, reproductive, and other disorders, have triggered significant interest for research. Benzophenones should be extracted from environmental samples and determined for environmental-monitoring purposes to assess their presence and possible dangers. Numerous sample preparation methods for benzophenones in environmental matrices and industrial effluents have been proposed and their detection in more complex matrices, such as fish and sludges, has also been reported. These methods range from classical to more state-of-the-art methods, such as solid-phase extraction, dispersive SPE, LLE, SBSE, etc., and the analysis is mostly completed with liquid chromatography, using several detection modes. This review critically outlines sample preparation methods that have been proposed to date, for the extraction of benzophenones from simple and complex environmental matrices and for cleaning up sample extracts to eliminate potential interfering components that coexist therein. Moreover, it provides a brief overview of their occurrence, fate, and toxicity.


Subject(s)
Benzophenones , Ecosystem , Animals , Female , Humans , Benzophenones/chemistry , Chromatography, Liquid , Solid Phase Extraction , Specimen Handling
18.
Environ Pollut ; 324: 121342, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36828352

ABSTRACT

Benzophenone-type UV filters (BPs) are common in natural aquatic environments. They can cause endocrine disruption or other adverse effects once they enter the human body via the food chain or drinking water. The primary cause of BPs accumulation and toxicity is the transport of BPs into the human body. Functional group substitutions can have a significant impact on the interactions of BPs and transporters, resulting in a variety of impact effects. Therefore, we explored the interaction between human serum albumin (HSA, a typical transporter) and ten typical BPs [benzophenone (BP1), 2-hydroxybenzophenone (BP2), 4-hydroxybenzophenone (BP3), 2,2'-dihydroxybenzophenone (BP4), 2,4-dihydroxybenzophenone (BP5), 4,4'-dihydroxybenzophenone (BP6), 2,4,4'-trihydroxybenzophenone (BP7), 2,2',4,4'-tetrahydroxybenzophenone (BP8), 2-hydroxy-4-methoxybenzophenone (BP9), and 2,2'-dihydroxy-4-methoxybenzophenone (BP10)] to study the role of functional group substitutions in binding. The results showed that BPs could bind to HSA at site 2, with binding constants ranging from 2.01 × 103 to 4.57 × 105 L/mol. Compared to BP1, hydroxyl and methoxy substitutions enhanced the BPs-HSA binding. The combined effect of the number and site of hydroxyl substitution at BPs determined the binding strength between BPs and HSA. It was more accessible to bind HSA when BPs were substituted with para-hydroxyl (4-hydroxyl) groups than with ortho-hydroxyl (2-hydroxyl) groups. Moreover, the additional para-methoxy (4-methoxy) group increased the BP-HSA binding strength by approximately 47 times under the same hydroxyl substitution conditions. Theoretical calculations revealed that functional group substitutions increased the intermolecular binding force by increasing the negative electrostatic potential surface area of BPs, which significantly increased the electrostatic and dispersion forces between the BPs and HSA. This BPs-HSA binding decreased the α-helix of HSA and influenced the ratio of other secondary structures, including ß-sheet, ß-turn, and random coil of HSA. This study provides a theoretical and experimental foundation for understanding the human health risks associated with BPs.


Subject(s)
Benzophenones , Serum Albumin, Human , Humans , Benzophenones/chemistry , Protein Binding , Thermodynamics
19.
J Healthc Eng ; 2023: 8487380, 2023.
Article in English | MEDLINE | ID: mdl-36760836

ABSTRACT

Objective: To evaluate the mechanical properties of porous polyetherketoneketone (PEKK) meshes with different thicknesses, pore sizes, and porosities through finite element analysis to provide an optimal PEKK design for alveolar bone augmentation in the posterior mandibular region. Methods: A three-dimensional evaluation model of severe alveolar bone defects in the mandibular posterior was constructed based on cone beam computerized tomography (CBCT) data. Then, PEKK meshes with different structural designs were obtained. Two key parameters were set with different values: five levels of thickness (0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, and 0.6 mm) and three levels of pore size (1 mm, 2 mm, and 3 mm) with a corresponding porosity of 19.18%-42.67%. A 100 N physiological force was simultaneously loaded by finite element analysis (FEA), and the deformation and stress data were outputted for further analysis. Results: The deformation and stress of the PEKK meshes are negatively correlated with the changes in thickness and positively correlated with the changes in pore size. The FEA results show that the maximum deformation, equivalent stress, and maximum principal stress of the PEKK meshes are 0.168 mm-0.478 mm, 49.243 MPa-124.890 MPa, and 31.549 MPa-104.200 MPa, respectively. The PEKK mesh group with a thickness of 0.2 mm, pore size of 3 mm, and porosity of 42.67% is in danger of plastic deformation or even fracture during use. Conclusion: According to the FEA results, the PEKK meshes with larger thicknesses and smaller pore sizes and porosities behave better. In consideration of reducing soft tissue stimulation and promoting bone regeneration, an ultrathin porous PEKK mesh with a pore size of no more than 3 mm, porosity of no more than 42.67%, and thickness of 0.2 mm can be used clinically to meet the mechanical performance requirements of the guided bone regeneration (GBR) structure.


Subject(s)
Polymers , Surgical Mesh , Humans , Finite Element Analysis , Polymers/chemistry , Benzophenones/chemistry
20.
J Hazard Mater ; 446: 130634, 2023 03 15.
Article in English | MEDLINE | ID: mdl-36599278

ABSTRACT

Ten common benzophenone-based UV filters (BPs), sharing the same basic structure and differing only in their substituents, were investigated with respect to their primary and ultimate biodegradability. This study was carried out in order to gain deeper insights into the relationship between structure and biodegradability. The primary biodegradation of the selected BPs was studied in river water at environmentally relevant concentrations (1 µg/L) while varying specific, crucial environmental conditions (aerobic, suboxic, supplementation of nutrients). For this purpose, both batch and column degradation tests were performed, which allowed a systematic study of the effects. Subsequently, the ultimate biodegradation, i.e. the potential to achieve full mineralization of BPs, was examined according to OECD guideline 301 F. The results indicate that mineralization is limited to derivatives in which both aromatic rings contain substituents. This hypothesis was supported by docking simulations showing systematic differences in the orientation of BPs within the active site of the cytochrome P450 enzyme. These differences in orientation correspond to the substitution pattern of the BPs. This study provides valuable insights for assessing the environmental hazards of this class of trace organic compounds.


Subject(s)
Benzophenones , Water Pollutants, Chemical , Benzophenones/chemistry , Biodegradation, Environmental , Fresh Water , Water Pollutants, Chemical/analysis
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