Molecules

23 pages, 12483 KiB

Open AccessArticle

Development of Resorbable Phosphate-Based Glass Microspheres as MRI Contrast Media Agents

by Jesús Molinar-Díaz, Andi Arjuna, Nichola Abrehart, Alison McLellan, Roy Harris, Md Towhidul Islam, Ahlam Alzaidi, Chris R. Bradley, Charlotte Gidman, Malcolm J. W. Prior, Jeremy Titman, Nicholas P. Blockley, Peter Harvey, Luca Marciani and Ifty Ahmed

Molecules 2024, 29(18), 4296; https://doi.org/10.3390/molecules29184296 (registering DOI) - 10 Sep 2024

Abstract

In this research, resorbable phosphate-based glass (PBG) compositions were developed using varying modifier oxides including iron (Fe₂O₃), copper (CuO), and manganese (MnO₂), and then processed via a rapid single-stage flame spheroidisation process to manufacture dense (i.e., solid) [...] Read more.

In this research, resorbable phosphate-based glass (PBG) compositions were developed using varying modifier oxides including iron (Fe₂O₃), copper (CuO), and manganese (MnO₂), and then processed via a rapid single-stage flame spheroidisation process to manufacture dense (i.e., solid) and highly porous microspheres. Solid (63–200 µm) and porous (100–200 µm) microspheres were produced and characterised via SEM, XRD, and EDX to investigate their surface topography, structural properties, and elemental distribution. Complementary NMR investigations revealed the formation of Q², Q¹, and Q⁰ phosphate species within the porous and solid microspheres, and degradation studies performed to evaluate mass loss, particle size, and pH changes over 28 days showed no significant differences among the microspheres (63–71 µm) investigated. The microspheres produced were then investigated using clinical (1.5 T) and preclinical (7 T) MRI systems to determine the R₁ and R₂ relaxation rates. Among the compositions investigated, manganese-based porous and solid microspheres revealed enhanced levels of R₂ (9.7–10.5 s⁻¹ for 1.5 T; 17.1–18.9 s⁻¹ for 7 T) and R₁ (3.4–3.9 s⁻¹ for 1.5 T; 2.2–2.3 s⁻¹ for 7 T) when compared to the copper and iron-based microsphere samples. This was suggested to be due to paramagnetic ions present in the Mn-based microspheres. It is also suggested that the porosity in the resorbable PBG porous microspheres could be further explored for loading with drugs or other biologics. This would further advance these materials as MRI theranostic agents and generate new opportunities for MRI contrast-enhancement oral-delivery applications. Full article

(This article belongs to the Special Issue Advanced Magnetic Resonance Methods in Materials Chemistry Analysis)

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16 pages, 597 KiB

Open AccessArticle

Nickel-Catalyzed Three-Component 1,2-Carboacylation of Alkenes

by Shengzhou Jin, Lanfen Wang, Yinggang Jia, Wenbo Ma and Dingyi Wang

Molecules 2024, 29(18), 4295; https://doi.org/10.3390/molecules29184295 (registering DOI) - 10 Sep 2024

Abstract

Ketones, prevalent in many biologically significant molecules, require the development of novel methods to synthesize these structures, which is a critical endeavor in organic synthesis. Transition metal catalysis has proven to be an effective method for synthesizing ketones. However, the scope of these [...] Read more.

Ketones, prevalent in many biologically significant molecules, require the development of novel methods to synthesize these structures, which is a critical endeavor in organic synthesis. Transition metal catalysis has proven to be an effective method for synthesizing ketones. However, the scope of these substrates remains relatively limited, particularly due to their incompatibility with sensitive functional groups. Herein, we report a Ni-catalyzed three-component 1,2-carboacylation of alkenes, which activates secondary/tertiary alkyl bromides. This method offers significant advantages: simplicity of operation, ready availability of substrates, and broad substrate applicability. A series of experimental studies have helped clarify the key mechanistic pathways involved in this cascade reaction. Full article

(This article belongs to the Special Issue Recent Advances in Transition Metal Catalysis)

18 pages, 1034 KiB

Open AccessReview

Application of Intelligent Response Fluorescent Probe in Breast Cancer

by Anqi Sheng, Hao Zhang, Qing Li, Shu Chen and Qingshuang Wang

Molecules 2024, 29(18), 4294; https://doi.org/10.3390/molecules29184294 - 10 Sep 2024

Abstract

As one of the leading cancers threatening women’s lives and health, breast cancer is challenging to treat and often irreversible in advanced cases, highlighting the critical importance of early detection and intervention. In recent years, fluorescent probe technology, a revolutionary in vivo imaging [...] Read more.

As one of the leading cancers threatening women’s lives and health, breast cancer is challenging to treat and often irreversible in advanced cases, highlighting the critical importance of early detection and intervention. In recent years, fluorescent probe technology, a revolutionary in vivo imaging tool, has gained attention in medical research for its ability to improve tumor visualization significantly. This review focuses on recent advances in intelligent, responsive fluorescent probes, particularly in the field of breast cancer, which are divided into five categories, near-infrared responsive, fluorescein-labeled, pH-responsive, redox-dependent, and enzyme-triggered fluorescent probes, each of which has a different value for application based on its unique biological response mechanism. In addition, this review also covers the strategy of combining fluorescent probes with various anti-tumor drugs, aiming to reveal the possibility of synergistic effects between the two in breast cancer treatment and provide a solid theoretical platform for the clinical translation of fluorescent probe technology, which is expected to promote the expansion of cancer treatment technology. Full article

(This article belongs to the Special Issue Advanced Luminescent Materials: From Design, Synthesis, Fluorescent Mechanism to Applications)

25 pages, 9813 KiB

Open AccessArticle

The Importance of Biotinylation for the Suitability of Cationic and Neutral Fourth-Generation Polyamidoamine Dendrimers as Targeted Drug Carriers in the Therapy of Glioma and Liver Cancer

by Łukasz Uram, Magdalena Twardowska, Żaneta Szymaszek, Maria Misiorek, Andrzej Łyskowski, Zuzanna Setkowicz, Zuzanna Rauk and Stanisław Wołowiec

Molecules 2024, 29(18), 4293; https://doi.org/10.3390/molecules29184293 (registering DOI) - 10 Sep 2024

Abstract

In this study, we hypothesized that biotinylated and/or glycidol-flanked fourth-generation polyamidoamine (PAMAM G4) dendrimers could be a tool for efficient drug transport into glioma and liver cancer cells. For this purpose, native PAMAM (G4) dendrimers, biotinylated (G4B), glycidylated (G4gl), and biotinylated and glycidylated [...] Read more.

In this study, we hypothesized that biotinylated and/or glycidol-flanked fourth-generation polyamidoamine (PAMAM G4) dendrimers could be a tool for efficient drug transport into glioma and liver cancer cells. For this purpose, native PAMAM (G4) dendrimers, biotinylated (G4B), glycidylated (G4gl), and biotinylated and glycidylated (G4Bgl), were synthesized, and their cytotoxicity, uptake, and accumulation in vitro and in vivo were studied in relation to the transport mediated by the sodium-dependent multivitamin transporter (SMVT). The studies showed that the human temozolomide-resistant glioma cell line (U-118 MG) and hepatocellular carcinoma cell line (HepG2) indicated a higher amount of SMVT than human HaCaT keratinocytes (HaCaTs) used as a model of normal cells. The G4gl and G4Bgl dendrimers were highly biocompatible in vitro (they did not affect proliferation and mitochondrial activity) against HaCaT and U-118 MG glioma cells and in vivo (against Caenorhabditis elegans and Wistar rats). The studied compounds penetrated efficiently into all studied cell lines, but inconsistently with the uptake pattern observed for biotin and disproportionately for the level of SMVT. G4Bgl was taken up and accumulated after 48 h to the highest degree in glioma U-118 MG cells, where it was distributed in the whole cell area, including the nuclei. It did not induce resistance symptoms in glioma cells, unlike HepG2 cells. Based on studies on Wistar rats, there are indications that it can also penetrate the blood–brain barrier and act in the central nervous system area. Therefore, it might be a promising candidate for a carrier of therapeutic agents in glioma therapy. In turn, visualization with a confocal microscope showed that biotinylated G4B penetrated efficiently into the body of C. elegans, and it may be a useful vehicle for drugs used in anthelmintic therapy. Full article

(This article belongs to the Special Issue Anticancer Drug Discovery and Development II)

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8 pages, 513 KiB

Open AccessCommunication

Secobutanolides Isolated from Lindera obtusiloba Stem and Their Anti-Inflammatory Activity

by Hye Jin Yang, Young-Sang Koh, MinKyun Na and Wei Li

Molecules 2024, 29(18), 4292; https://doi.org/10.3390/molecules29184292 - 10 Sep 2024

Abstract

In this study, a new secobutanolide, named secosubamolide B (3), along with three previously known secobutanolides (1, 2, and 4), were successfully isolated from a methanol extract of the stem of Lindera obtusiloba. The chemical structures [...] Read more.

In this study, a new secobutanolide, named secosubamolide B (3), along with three previously known secobutanolides (1, 2, and 4), were successfully isolated from a methanol extract of the stem of Lindera obtusiloba. The chemical structures of these compounds were elucidated through the analysis of spectroscopic data, and then compared with the existing literature to confirm their identities. Furthermore, the anti-inflammatory effect of these isolated compounds on bone marrow-derived dendritic cells stimulated by lipopolysaccharide (LPS) was evaluated. Compounds 1–3 showed the significant suppression of LPS-triggered IL-6 and IL-12 p40 production, with IC₅₀ values between 1.8 and 24.1 µM. These findings may provide a scientific foundation for developing anti-inflammatory agents from L. obtusiloba. Full article

(This article belongs to the Special Issue Secondary Metabolites from Natural Products: Extraction, Isolation and Biological Activities)

27 pages, 1056 KiB

Open AccessArticle

Acetylation of Oleanolic Acid Dimers as a Method of Synthesis of Powerful Cytotoxic Agents

by Andrzej Günther, Przemysław Zalewski, Szymon Sip, Piotr Ruszkowski and Barbara Bednarczyk-Cwynar

Molecules 2024, 29(18), 4291; https://doi.org/10.3390/molecules29184291 - 10 Sep 2024

Abstract

Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention in the scientific community due to its diverse pharmacological properties. Continuing our previous work on the synthesis of oleanolic acid dimers (OADs), a simple, economical, and safe acetylation reaction was performed. The [...] Read more.

Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention in the scientific community due to its diverse pharmacological properties. Continuing our previous work on the synthesis of oleanolic acid dimers (OADs), a simple, economical, and safe acetylation reaction was performed. The newly obtained derivatives (AcOADs, 3a–3n) were purified using two methods. The structures of all acetylated dimers (3a–3n) were determined based on spectral methods (IR, NMR). For all AcOADs (3a–3n), the relationship between the structure and the expected directions of pharmacological activity was determined using a computational method (QSAR computational analysis). All dimers were also tested for their cytotoxic activity on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines. HDF cell line was applied to evaluate the Selectivity Index of the tested compounds. All cytotoxic tests were performed with the application of the MTT assay. Finally, all dimers of oleanolic acid were subjected to DPPH and CUPRAC tests to evaluate their antioxidant activity. The obtained results indicate a very high level of cytotoxic activity (IC₅₀ for most AcOADs below 5.00 µM) and a fairly high level of antioxidant activity (Trolox equivalent in some cases above 0.04 mg/mL). Full article

(This article belongs to the Special Issue Recent Advances in Development of Small Molecules to Fight Cancer—2nd Edition)

12 pages, 415 KiB

Open AccessArticle

A Novel High Performance Liquid Chromatography Method for Camphor Determination and Application in Cosmetics and Pharmaceuticals: Development and Validation

by Martin Lalić, Ana Soldić, Zdenka Lalić and Miranda Sertić

Molecules 2024, 29(18), 4290; https://doi.org/10.3390/molecules29184290 - 10 Sep 2024

Abstract

A novel high-performance liquid chromatography (HPLC) method with 4-N,N-dimethylaminobenzaldehyde as an internal standard was developed for the determination of Camphor with the main goal of facilitating the analysis of different cosmetic and pharmaceutical products that contain Camphor in analytical [...] Read more.

A novel high-performance liquid chromatography (HPLC) method with 4-N,N-dimethylaminobenzaldehyde as an internal standard was developed for the determination of Camphor with the main goal of facilitating the analysis of different cosmetic and pharmaceutical products that contain Camphor in analytical laboratories. The method can be applied to cosmetic and pharmaceutical samples such as gels, ointments, and creams containing Camphor. Chromatographic separation was carried out on the Symmetry^® C18, 5 μm column (Waters), 250 × 4.6 equipped with guard column E, InertSustain C18, 5 µm, while using the flow of 1.4 mL/min, with a column temperature of 25 °C. The mobile phase consisted of 600 mL of acetonitrile, 400 mL of purified water, and 6 mL of glacial acetic acid. The method was evaluated in accordance with ICH Q2 (R2) guidelines for validation parameters: selectivity, linearity (range 0.10–3.00 mg/mL), the limit of detection (LOD = 0.028 mg/mL), the limit of quantification (LOQ = 0.085 mg/mL), accuracy (confidence intervals < 0.05%), repeatability (peak area ratio = 0.39–1.97), and intermediate precision (peak area ratio = 0.40–1.98). The method is applicable for detecting and quantifying Camphor in a variety of cosmetic and pharmaceutical products from different parts of the world, thus covering the concentrations required by different law legislations. Full article

(This article belongs to the Section Analytical Chemistry)

18 pages, 5326 KiB

Open AccessArticle

Fabrication of PLA-Based Nanoneedle Patches Loaded with Transcutol-Modified Chitosan Nanoparticles for the Transdermal Delivery of Levofloxacin

by Christina Samiotaki, Ioanna Koumentakou, Evi Christodoulou, Nikolaos D. Bikiaris, Marilena Vlachou, Evangelos Karavas, Konstantina Tourlouki, Nikolaos Kehagias and Panagiotis Barmpalexis

Molecules 2024, 29(18), 4289; https://doi.org/10.3390/molecules29184289 - 10 Sep 2024

Abstract

Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. [...] Read more.

Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. Chitosan was chemically modified with transcutol in three ratios (1/1, 1/2, 1/3, w/w), and the optimum ratio was used for nanoparticle fabrication via the ionic gelation method. The successful modification was confirmed using ATR-FTIR spectroscopy, while DLS results revealed that only the 1/3 ratio afforded suitably sized particles of 220 nm. After drug encapsulation, the particle size increased to 435 nm, and the final formulations were examined via XRD and an in vitro dissolution test, which suggested that the nanoparticles reach 60% release in a monophasic pattern at 380 h. We then prepared transdermal patches with pyramidal geometry nanoneedles using different poly(lactic acid)/poly(ethylene adipate) (PLA/PEAd) polymer blends of varying ratios, which were characterized in terms of morphology and mechanical compressive strength. The 90/10 blend exhibited the best mechanical properties and was selected for further testing. Ex vivo permeation studies proved that the nanoneedle patches containing drug-loaded nanoparticles achieved the highest levofloxacin permeation (88.1%). Full article

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23 pages, 4038 KiB

Open AccessArticle

Spectroscopic Relationship between XOD and TAOZHI Total Polyphenols Based on Chemometrics and Molecular Docking Techniques

by Mingyu Yang, Yitang Xu, Qihua Yu, Mengyu Li, Liyong Yang and Ye Yang

Molecules 2024, 29(18), 4288; https://doi.org/10.3390/molecules29184288 - 10 Sep 2024

Abstract

Xanthine oxidase (XOD) is a key enzyme that promotes the oxidation of xanthine/hypoxanthine to form uric acid, and the accumulation of uric acid leads to hyperuricaemia. The prevalence of gout caused by hyperuricaemia is increasing year by year. TAOZHI (TZ) can be used [...] Read more.

Xanthine oxidase (XOD) is a key enzyme that promotes the oxidation of xanthine/hypoxanthine to form uric acid, and the accumulation of uric acid leads to hyperuricaemia. The prevalence of gout caused by hyperuricaemia is increasing year by year. TAOZHI (TZ) can be used for the treatment of rheumatic arthralgia due to qi stagnation and blood stasis and contains a large number of polyphenolic components. The aim of this study was to investigate the relationship between chromatograms and XOD inhibition of 21 batches of TZ total polyphenol extract samples. Chemometric methods such as grey correlation analysis, bivariate correlation analysis, and partial least squares regression were used to identify the active ingredient groups in the total polyphenol extracts of TZ, which were validated using molecular docking techniques. The total polyphenol content contained in the 21 batches did not differ significantly, and all batches showed inhibitory effects on XOD. Spectroeffect correlation analysis showed that the inhibitory effect of TZ on XOD activity was the result of the synergistic effect of multiple components, and the active component groups screened to inhibit XOD were F2 (4-O-Caffeoylquinic acid), F4, and F10 (naringenin). The molecular docking results showed that the binding energies of all nine dockings were lower than −7.5 kcal/mol, and the binding modes included hydrogen bonding, hydrophobic forces, salt bridges, and π-staking, and the small molecules might exert their pharmacological effects by binding to XOD through the residue sites of the amino acids, such as threonine, arginine, and leucine. This study provides some theoretical basis for the development and utilisation of TZ total polyphenols. Full article

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13 pages, 4429 KiB

Open AccessArticle

Photo-Thermal Conversion and Raman Sensing Properties of Three-Dimensional Gold Nanostructure

by Feng Shan, Jingyi Huang, Yanyan Zhu and Guohao Wei

Molecules 2024, 29(18), 4287; https://doi.org/10.3390/molecules29184287 - 10 Sep 2024

Abstract

Three-dimensional plasma nanostructures with high light–thermal conversion efficiency show the prospect of industrialization in various fields and have become a research hotspot in areas of light–heat utilization, solar energy capture, and so on. In this paper, a simple chemical synthesis method is proposed [...] Read more.

Three-dimensional plasma nanostructures with high light–thermal conversion efficiency show the prospect of industrialization in various fields and have become a research hotspot in areas of light–heat utilization, solar energy capture, and so on. In this paper, a simple chemical synthesis method is proposed to prepare gold nanoparticles, and the electrophoretic deposition method is used to assemble large-area three-dimensional gold nanostructures (3D-GNSs). The light–thermal water evaporation monitoring and surface-enhanced Raman scattering (SERS) measurements of 3D-GNSs were performed via theoretical simulation and experiments. We reveal the physical processes of local electric field optical enhancement and the light–thermal conversion of 3D-GNSs. The results show that with the help of the efficient optical trapping and super-hydrophilic surface properties of 3D-GNSs, they have a significant effect in accelerating water evaporation, which was increased by nearly eight times. At the same time, the three-dimensional SERS substrates based on gold nanosphere particles (GNSPs) and gold nanostar particles (GNSTs) had limited sensitivities of 10⁻¹⁰ M and 10⁻¹² M to R6G molecules, respectively. Therefore, 3D-GNSs show strong competitiveness in the fields of solar-energy-induced water purification and the Raman trace detection of organic molecules. Full article

(This article belongs to the Special Issue Raman Spectroscopy Analysis of Surfaces)

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20 pages, 5506 KiB

Open AccessArticle

Synthesis, Surface Activity, Emulsifiability and Bactericidal Performance of Zwitterionic Tetrameric Surfactants

by Xin Wei, Jie Li, Xiangfei Geng, Di Niu, Zhenjie Wei, Chenxu Wang, Ziqi Sun and Yangchun Xie

Molecules 2024, 29(18), 4286; https://doi.org/10.3390/molecules29184286 - 10 Sep 2024

Abstract

In this paper, a series of tetrameric surfactants (4C_nSAZs, n = 12, 14, 16) endowed with zwitterionic characteristic were synthesized by a simple and convenient method and their structures were characterized by FT-IR, ¹H NMR and elemental analysis. Their physicochemical [...] Read more.

In this paper, a series of tetrameric surfactants (4C_nSAZs, n = 12, 14, 16) endowed with zwitterionic characteristic were synthesized by a simple and convenient method and their structures were characterized by FT-IR, ¹H NMR and elemental analysis. Their physicochemical properties were studied using the Wilhelmy plate method, fluorescence spectra and dynamic light scattering technique. 4C_nSAZs have higher surface activities and tend to adsorb at the air/water surface rather than self-assembling in aqueous solution. The thermodynamic parameters obtained from surface tension measurements show that both processes of adsorption and micellization of 4C_nSAZs are spontaneous and that the micellization processes of 4C_nSAZs are entropy-driven processes. Both adsorption and micellization of 4C_nSAZs are inclined to occur with the increase of alkyl chain length or temperature. For 4C₁₂SAZs, there are only small-size aggregates (micelles), while the large aggregates (vesicles) are observed at the alkyl length of 4C_nSAZs of 14 or 16. This shows that the alkyl chain length for oligomeric surfactants has a greater sensitivity for aggregate growth. The aggregate morphologies obtained from the calculated values of critical packing parameter (p) for 4C₁₄SAZs and 4C₁₆SAZs can be supported by the DLS measurement results. The test results obtained by the separation-water-time method show that 4C_nSAZs have good emulsification performance and that the prepared emulsions appear to exit in the form of multiple emulsions. In addition, 4C_nSAZs have good antibacterial activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The present study reveals the unique behavior of a zwitterionic tetrameric surfactant and may give new insights into molecular design and synthesis of a high degree of surfactants with different structure characteristics for potential application in various industrial fields. Full article

(This article belongs to the Special Issue Surfactants at Liquid Interfaces: Applications in Enhanced Oil Recovery)

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22 pages, 6913 KiB

Open AccessArticle

Novel Autotaxin Inhibitor ATX-1d Significantly Enhances Potency of Paclitaxel—An In Silico and In Vitro Study

by Prateek Rai, Christopher J. Clark, Carl B. Womack, Curtis Dearing, Joshua Thammathong, Derek D. Norman, Gábor J. Tigyi, Subhabrata Sen, Kevin Bicker, April M. Weissmiller and Souvik Banerjee

Molecules 2024, 29(18), 4285; https://doi.org/10.3390/molecules29184285 - 10 Sep 2024

Abstract

The development of drug resistance in cancer cells poses a significant challenge for treatment, with nearly 90% of cancer-related deaths attributed to it. Over 50% of ovarian cancer patients and 30–40% of breast cancer patients exhibit resistance to therapies such as Taxol. Previous [...] Read more.

The development of drug resistance in cancer cells poses a significant challenge for treatment, with nearly 90% of cancer-related deaths attributed to it. Over 50% of ovarian cancer patients and 30–40% of breast cancer patients exhibit resistance to therapies such as Taxol. Previous literature has shown that cytotoxic cancer therapies and ionizing radiation damage tumors, prompting cancer cells to exploit the autotaxin (ATX)–lysophosphatidic acid (LPA)–lysophosphatidic acid receptor (LPAR) signaling axis to enhance survival pathways, thus reducing treatment efficacy. Therefore, targeting this signaling axis has become a crucial strategy to overcome some forms of cancer resistance. Addressing this challenge, we identified and assessed ATX-1d, a novel compound targeting ATX, through computational methods and in vitro assays. ATX-1d exhibited an IC₅₀ of 1.8 ± 0.3 μM for ATX inhibition and demonstrated a significant binding affinity for ATX, as confirmed by MM-GBSA, QM/MM-GBSA, and SAPT in silico methods. ATX-1d significantly amplified the potency of paclitaxel, increasing its effectiveness tenfold in 4T1 murine breast carcinoma cells and fourfold in A375 human melanoma cells without inducing cytotoxic effects as a single agent. Full article

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20 pages, 4378 KiB

Open AccessArticle

Effective Detoxification of Olive Mill Wastewater Using Multi-Step Surfactant-Based Treatment: Assessment of Environmental and Health Impact

by Yazan Akkam, Mohammad Zaitoun, Islam Aljarrah, Aiman Jaradat, Ali Hmedat, Hassan Alhmoud, Taha Rababah, Ali Almajwal and Numan Al-Rayyan

Molecules 2024, 29(18), 4284; https://doi.org/10.3390/molecules29184284 - 10 Sep 2024

Abstract

Olive mill wastewater (OMW) poses a significant environmental challenge and health concern in olive-producing countries, including Jordan. Surfactant micelles are frequently employed as solubilizing agents to enhance the water solubility of chemical compounds. This study aims to leverage the sodium dodecyl sulfate (SDS) [...] Read more.

Olive mill wastewater (OMW) poses a significant environmental challenge and health concern in olive-producing countries, including Jordan. Surfactant micelles are frequently employed as solubilizing agents to enhance the water solubility of chemical compounds. This study aims to leverage the sodium dodecyl sulfate (SDS) micelles in a multi-step process to detoxify OMW for agricultural and industrial uses and reduce its impact. The OMW was treated in multiple steps: screening, coagulation with different chemicals, and distillation with different surfactants. The treatment steps were monitored using LC–MS, GC–MS, ICP–MS, chemical oxygen demand contents, and total phenolic compounds. The detoxification of OMW was evaluated using standard germination assays, MTT assays using tissue culture, and toxicity assays using fluorescence bacteria. Following the treatment, the seed growth rate improved significantly from 0% to 100%. The GC–MS revealed a substantial decrease in pollutants. The concentration of polyphenols was reduced to 2.5%, while the COD level decreased to 35%. The toxicity in bacteria was significantly reduced in a time-dependent manner, and the toxicity in human cells decreased by 95%. Additionally, between 50% and 95% of metals in OMW were removed. The multi-step SDS-based approach successfully detoxified the OMW and enhanced water quality, which would pave the road for its direct application in industry and agriculture. Full article

(This article belongs to the Special Issue Adsorbents in Treatment of Pollutants)

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21 pages, 841 KiB

Open AccessReview

The Aryl Hydrocarbon Receptor and Its Crosstalk: A Chemopreventive Target of Naturally Occurring and Modified Phytochemicals

by Hanna Szaefer, Barbara Licznerska and Wanda Baer-Dubowska

Molecules 2024, 29(18), 4283; https://doi.org/10.3390/molecules29184283 - 10 Sep 2024

Abstract

The aryl hydrocarbon receptor (AhR) is an environmentally sensitive transcription factor (TF) historically associated with carcinogenesis initiation via the activation of numerous carcinogens. Nowadays, the AhR has been attributed to multiple endogenous functions to maintain cellular homeostasis. Moreover, crosstalk, often reciprocal, has been [...] Read more.

The aryl hydrocarbon receptor (AhR) is an environmentally sensitive transcription factor (TF) historically associated with carcinogenesis initiation via the activation of numerous carcinogens. Nowadays, the AhR has been attributed to multiple endogenous functions to maintain cellular homeostasis. Moreover, crosstalk, often reciprocal, has been found between the AhR and several other TFs, particularly estrogen receptors (ERs) and nuclear factor erythroid 2-related factor-2 (Nrf2). Adequate modulation of these signaling pathways seems to be an attractive strategy for cancer chemoprevention. Several naturally occurring and synthetically modified AhR or ER ligands and Nrf2 modulators have been described. Sulfur-containing derivatives of glucosinolates, such as indole-3-carbinol (I3C), and stilbene derivatives are particularly interesting in this context. I3C and its condensation product, 3,3′-diindolylmethane (DIM), are classic examples of blocking agents that increase drug-metabolizing enzyme activity through activation of the AhR. Still, they also affect multiple essential signaling pathways in preventing hormone-dependent cancer. Resveratrol is a competitive antagonist of several classic AhR ligands. Its analogs, with ortho-methoxy substituents, exert stronger antiproliferative and proapoptotic activity. In addition, they modulate AhR activity and estrogen metabolism. Their activity seems related to a number of methoxy groups introduced into the stilbene structure. This review summarizes the data on the chemopreventive potential of these classes of phytochemicals, in the context of AhR and its crosstalk modulation. Full article

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25 pages, 8632 KiB

Open AccessArticle

Rational Design, Synthesis, Molecular Docking, and Biological Evaluations of New Phenylpiperazine Derivatives of 1,2-Benzothiazine as Potential Anticancer Agents

by Berenika M. Szczęśniak-Sięga, Natalia Zaręba, Żaneta Czyżnikowska, Tomasz Janek and Marta Kepinska

Molecules 2024, 29(18), 4282; https://doi.org/10.3390/molecules29184282 - 10 Sep 2024

Abstract

The aim of this study was to obtain new, safe, and effective compounds with anticancer activity since cancer is still the leading cause of mortality worldwide. The rational design of new compounds was based on the introduction of differentially substituted phenylpiperazines into the [...] Read more.

The aim of this study was to obtain new, safe, and effective compounds with anticancer activity since cancer is still the leading cause of mortality worldwide. The rational design of new compounds was based on the introduction of differentially substituted phenylpiperazines into the 1,2-benzothiazine scaffold as a reference for the structures of recent topoisomerase II (Topo II) inhibitors such as dexrazoxane and XK-469. The newly designed group of 1,2-benzothiazine derivatives was synthesized and tested on healthy (MCF10A) and cancer (MCF7) cell lines, alone and in combination with doxorubicin (DOX). In addition, molecular docking studies were performed both to the DNA-Topo II complex and to the minor groove of DNA. Most of the tested compounds showed cytotoxic activity comparable to doxorubicin, a well-known anticancer drug. The compound BS230 (3-(4-chlorobenzoyl)-2-{2-[4-(3,4-dichlorophenyl)-1-piperazinyl]-2-oxoethyl}-4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide) showed the best antitumor activity with lower cytotoxicity towards healthy cells and at the same time stronger cytotoxicity towards cancer cells than DOX. Moreover, molecular docking studies showed that BS230 has the ability to bind to both the DNA-Topo II complex and the minor groove of DNA. Binding of the minor groove to DNA was also proven by fluorescence spectroscopy. Full article

(This article belongs to the Special Issue Design, Synthesis and Applications of Bioactive Compounds)

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