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Heliyon May 2024We developed a novel chromogenic reagent and sensor by selective approach, for the detection and identification of dichlorvos, which we tested with the thin layer...
We developed a novel chromogenic reagent and sensor by selective approach, for the detection and identification of dichlorvos, which we tested with the thin layer chromatography method. For the first time, we reported in situ-generated glyoxal as a hydrolysis product, which then interacts with isoniazid to produce a yellow-colored cyclic compound. We used well-known spectroscopic techniques to confirm the chemical identity of the final product. We initially investigated the reaction using a variety of approaches, followed by attempts to establish the reaction mechanism using Density Functional Theory by Gaussian software.
PubMed: 38813177
DOI: 10.1016/j.heliyon.2024.e31217 -
Acta Pharmaceutica Sinica. B May 2024Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their...
Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S. After internalization of mB4S, EPI was acidic-responsively released to induce ICD, which was characterized by an increased level of calreticulin (CRT) exposure and enhanced ATP secretion. Meanwhile, diABZI effectively activated the STING pathway. Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells (DCs) and CD8 T cells, promoting cytokines secretion, up-regulating M1-like tumor-associated macrophages (TAMs) and down-regulating immunosuppressive myeloid-derived suppressor cells (MDSCs). Therefore, this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8 T cells infiltration, creating an immuno-supportive microenvironment, thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.
PubMed: 38799622
DOI: 10.1016/j.apsb.2024.02.006 -
Molecules (Basel, Switzerland) May 2024(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing...
(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC varying from 40 to 60 μM after 48 h and between 13 and 20 μM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.
Topics: Humans; Tubulin; Cell Proliferation; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Benzimidazoles; Antineoplastic Agents; Female; Hydrazones; Molecular Docking Simulation; Tubulin Modulators; Structure-Activity Relationship; Polymerization; Molecular Structure
PubMed: 38792260
DOI: 10.3390/molecules29102400 -
Molecules (Basel, Switzerland) May 2024Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment...
Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine-Hydrazide Hydrazone Derivative.
Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from and cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.
Topics: Humans; Tamoxifen; Breast Neoplasms; MCF-7 Cells; Female; Aziridines; Apoptosis; Cell Proliferation; Cell Survival; Hydrazones; Probiotics; Antineoplastic Agents; Cell Cycle
PubMed: 38792153
DOI: 10.3390/molecules29102292 -
Molecules (Basel, Switzerland) May 2024The research on new compounds against plant pathogens is still socially and economically important. It results from the increasing resistance of pests to plant...
4-Hydroxybenzoic Acid-Based Hydrazide-Hydrazones as Potent Growth Inhibition Agents of Laccase-Producing Phytopathogenic Fungi That Are Useful in the Protection of Oilseed Crops.
The research on new compounds against plant pathogens is still socially and economically important. It results from the increasing resistance of pests to plant protection products and the need to maintain high yields of crops, particularly oilseed crops used to manufacture edible and industrial oils and biofuels. We tested thirty-five semi-synthetic hydrazide-hydrazones with aromatic fragments of natural origin against phytopathogenic laccase-producing fungi such as , , and . Among the investigated molecules previously identified as potent laccase inhibitors were also strong antifungal agents against the fungal species tested. The highest antifungal activity showed derivatives of 4-hydroxybenzoic acid and salicylic aldehydes with 3--butyl, phenyl, or isopropyl substituents. appeared to be the most susceptible to the tested compounds, with the lowest IC values between 0.5 and 1.8 µg/mL. We applied two variants of phytotoxicity tests for representative crop seeds and selected hydrazide-hydrazones. Most tested molecules show no or low phytotoxic effect for flax and sunflower seeds. Moreover, a positive impact on seed germination infected with fungi was observed. With the potential for application, the cytotoxicity of the hydrazide-hydrazones of choice toward MCF-10A and BALB/3T3 cell lines was lower than that of the azoxystrobin fungicide tested.
Topics: Hydrazones; Laccase; Crops, Agricultural; Antifungal Agents; Ascomycota; Animals; Plant Diseases; Hydroxybenzoates; Botrytis; Humans; Mice; Parabens
PubMed: 38792074
DOI: 10.3390/molecules29102212 -
Chemical Science May 2024Catalysts generated by the combination of pyridine-hydrazone ,-ligands and Pd(TFA) have been applied to the addition of arylboronic acids to formylphosphonate-derived...
Catalysts generated by the combination of pyridine-hydrazone ,-ligands and Pd(TFA) have been applied to the addition of arylboronic acids to formylphosphonate-derived hydrazones, yielding α-aryl α-hydrazino phosphonates in excellent enantioselectivities (96 → 99% ee). Subsequent removal of the benzyloxycarbonyl (Cbz) -protecting group afforded key building blocks en route to appealing artificial peptides, herbicides and antitumoral derivatives. Experimental and computational data support a stereochemical model based on aryl-palladium intermediates in which the phosphono hydrazone coordinates in its -configuration, maximizing the interactions between the substrate and the pyridine-hydrazone ligand.
PubMed: 38784752
DOI: 10.1039/d4sc00822g -
BioRxiv : the Preprint Server For... May 2024Dynamic covalent crosslinked (DCC) hydrogels represent a significant advance in biomaterials for regenerative medicine and mechanobiology. These gels typically offer...
Dynamic covalent crosslinked (DCC) hydrogels represent a significant advance in biomaterials for regenerative medicine and mechanobiology. These gels typically offer viscoelasticity and self-healing properties that more closely mimic tissue mechanics than traditional, predominantly elastic, covalent crosslinked hydrogels. Despite their promise, the effects of varying crosslinker architecture - side chain versus telechelic crosslinks - on the viscoelastic properties of DCC hydrogels have not been thoroughly investigated. This study introduces hydrazone-based alginate hydrogels and examines how side-chain and telechelic crosslinker architectures impact hydrogel viscoelasticity and stiffness. In side-chain crosslinked gels, higher polymer concentrations, enhances stiffness and decelerates stress relaxation, while an off-stoichiometric hydrazine-to-aldehyde ratio leads to reduced stiffness and shorter relaxation time. In telechelic crosslinked gels, maximal stiffness and stress relaxation occurs at intermediate crosslinker concentrations for both linear and star crosslinkers, with higher crosslinker valency further increasing stiffness and decreasing relaxation rates. Our result suggested different ranges of stiffness and stress relaxation are accessible with the different crosslinker architectures, with side-chain crosslinking leading to gels with slower stress relaxation times relative to the other architectures, and star crosslinked gels providing increased stiffness and slower stress relaxation relative to linear crosslinked gels. The mechanical properties of hydrogels with star crosslinking are more robust to changes induced by competing chemical reactions compared to linear crosslinking. Our research underscores the pivotal role of crosslinker architecture in defining hydrogel stiffness and viscoelasticity, providing crucial insights for the design of DCC hydrogels with tailored mechanical properties for specific biomedical applications.
PubMed: 38766044
DOI: 10.1101/2024.05.07.593040 -
Carbohydrate Polymers Aug 2024The dynamic interplay between cells and their native extracellular matrix (ECM) influences cellular behavior, imposing a challenge in biomaterial design. Dynamic...
The dynamic interplay between cells and their native extracellular matrix (ECM) influences cellular behavior, imposing a challenge in biomaterial design. Dynamic covalent hydrogels are viscoelastic and show self-healing ability, making them a potential scaffold for recapitulating native ECM properties. We aimed to implement kinetically and thermodynamically distinct crosslinkers to prepare self-healing dynamic hydrogels to explore the arising properties and their effects on cellular behavior. To do so, aldehyde-substituted hyaluronic acid (HA) was synthesized to generate imine, hydrazone, and oxime crosslinked dynamic covalent hydrogels. Differences in equilibrium constants of these bonds yielded distinct properties including stiffness, stress relaxation, and self-healing ability. The effects of degree of substitution (DS), polymer concentration, crosslinker to aldehyde ratio, and crosslinker functionality on hydrogel properties were evaluated. The self-healing ability of hydrogels was investigated on samples of the same and different crosslinkers and DS to obtain hydrogels with gradient properties. Subsequently, human dermal fibroblasts were cultured in 2D and 3D to assess the cellular response considering the dynamic properties of the hydrogels. Moreover, assessing cell spreading and morphology on hydrogels having similar modulus but different stress relaxation rates showed the effects of matrix viscoelasticity with higher cell spreading in slower relaxing hydrogels.
Topics: Hyaluronic Acid; Hydrogels; Humans; Fibroblasts; Schiff Bases; Cross-Linking Reagents; Biocompatible Materials; Extracellular Matrix; Cells, Cultured
PubMed: 38763720
DOI: 10.1016/j.carbpol.2024.122173 -
Scientific Reports May 2024A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were...
A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by HNMR, CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC = 12.84 ± 0.52 µM), 4 (IC = 13.64 ± 0.58 µM), 12 (IC = 15.73 ± 0.71 µM), 13 (IC = 16.62 ± 0.47 µM), 15 (IC = 17.40 ± 0.74 µM), 3 (IC = 18.45 ± 1.21 µM), 7 (IC = 19.68 ± 0.82 µM), and 2 (IC = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.
Topics: Molecular Docking Simulation; Glycoside Hydrolase Inhibitors; alpha-Glucosidases; 3,4-Dihydroxyphenylacetic Acid; Drug Design; Schiff Bases; Hydrazones; Structure-Activity Relationship
PubMed: 38762658
DOI: 10.1038/s41598-024-62034-x -
ACS Omega May 2024The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and...
The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are linked with various disorders including Alzheimer's disease. In this study, six new nicotinic hydrazide derivatives (-) were designed and synthesized for the first time, and their inhibitory profiles against hCA I, hCA II, AChE, and BChE were investigated by assays and studies. The structures of novel molecules were elucidated by using spectroscopic techniques and elemental analysis. These molecules showed inhibitory activities against hCA I and II with IC values ranging from 7.12 to 45.12 nM. Compared to reference drug acetazolamide (AZA), compound was the most active inhibitor against hCA I and II. On the other hand, it was determined that IC values of the tested molecules ranged between 21.45 and 61.37 nM for AChE and between 18.42 and 54.74 nM for BChE. Among them, compound was the most potent inhibitor of AChE and BChE, with IC values of 21.45 and 18.42 nM, respectively. In order to better understand the mode of action of these new compounds, state-of-the-art molecular modeling techniques were also conducted.
PubMed: 38737075
DOI: 10.1021/acsomega.3c10182