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Scientific Reports Jun 2024The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to...
The COVID-19 has had a significant influence on people's lives across the world. The viral genome has undergone numerous unanticipated changes that have given rise to new varieties, raising alarm on a global scale. Bioactive phytochemicals derived from nature and synthetic sources possess lot of potential as pathogenic virus inhibitors. The goal of the recent study is to report new inhibitors of Schiff bases of 1,3-dipheny urea derivatives against SARS COV-2 spike protein through in-vitro and in-silico approach. Total 14 compounds were evaluated, surprisingly, all the compounds showed strong inhibition with inhibitory values between 79.60% and 96.00% inhibition. Here, compounds 3a (96.00%), 3d (89.60%), 3e (84.30%), 3f (86.20%), 3g (88.30%), 3h (86.80%), 3k (82.10%), 3l (90.10%), 3m (93.49%), 3n (85.64%), and 3o (81.79%) exhibited high inhibitory potential against SARS COV-2 spike protein. While 3c also showed significant inhibitory potential with 79.60% inhibition. The molecular docking of these compounds revealed excellent fitting of molecules in the spike protein receptor binding domain (RBD) with good interactions with the key residues of RBD and docking scores ranging from - 4.73 to - 5.60 kcal/mol. Furthermore, molecular dynamics simulation for 150 ns indicated a strong stability of a complex 3a:6MOJ. These findings obtained from the in-vitro and in-silico study reflect higher potency of the Schiff bases of 1,3-diphenyl urea derivatives. Furthermore, also highlight their medicinal importance for the treatment of SARS COV-2 infection. Therefore, these small molecules could be a possible drug candidate.
Topics: Spike Glycoprotein, Coronavirus; Schiff Bases; SARS-CoV-2; Molecular Docking Simulation; Antiviral Agents; Urea; Molecular Dynamics Simulation; Humans; COVID-19 Drug Treatment; COVID-19
PubMed: 38822113
DOI: 10.1038/s41598-024-63345-9 -
Frontiers in Chemistry 2024[Cu(NN)]ClO is a copper (I) complex, where NN is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound...
[Cu(NN)]ClO is a copper (I) complex, where NN is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against , providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN)]ClO to over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In , an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In , both [Cu(NN)]ClO and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN)]ClO complex exhibited distinct effects on the intestinal microbiota of . In conclusion, our findings demonstrate that [Cu(NN)]ClO is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in .
PubMed: 38807978
DOI: 10.3389/fchem.2024.1338614 -
Journal of Inorganic Biochemistry May 2024Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal...
Four Pt(II) bis(pyrrole-imine) Schiff base chelates (1-4) were synthesised by previously reported methods, through a condensation reaction, and the novel crystal structure of 2,2'-{propane-1,3-diylbis[nitrilo(E)methylylidene]}bis(pyrrol-1-ido)platinum(II) (1) was obtained. Pt(II) complexes 1-4 exhibited phosphorescence, with increased luminescence in anaerobic solvents or when bound to human serum albumin (HSA). One of the complexes shows a 15.6-fold increase in quantum yield when bound to HSA and could be used to detect HSA concentrations as low as 5 nM. Pt(II) complexes 1-3 was investigated as potential theranostic agents in MCF-7 breast cancer cells, but only complex 3 exhibited cytotoxicity when irradiated with UV light (λ). Interestingly, the cytotoxicity of complex 1 was unresponsive to UV light irradiation. This indicates that only complex 3 can be considered a potential photosensitising agent.
PubMed: 38805758
DOI: 10.1016/j.jinorgbio.2024.112617 -
Molecules (Basel, Switzerland) May 2024The effective capture and recovery of radioiodine species associated with nuclear fuel reprocessing is of significant importance in nuclear power plants. Porous...
The effective capture and recovery of radioiodine species associated with nuclear fuel reprocessing is of significant importance in nuclear power plants. Porous materials have been proven to be one of the most effective adsorbents for the capture of radioiodine. In this work, we design and synthesize a series of conjugated microporous polymers (CMPs), namely, TPDA-TFPB CMP, TPDA-TATBA CMP, and TPDA-TECHO CMP, which are constructed based on a planar rectangular 4-connected organic monomer and three triangular 3-connected organic monomers, respectively. The resultant CMPs are characterized using various characterization techniques and used as effective adsorbents for iodine capture. Our experiments indicated that the CMPs exhibit excellent iodine adsorption capacities as high as 6.48, 6.25, and 6.37 g g at 348 K and ambient pressure. The adsorption mechanism was further investigated and the strong chemical adsorption between the iodine and the imine/tertiary ammonia of the CMPs, 3D network structure with accessible hierarchical pores, uniform micromorphology, wide π-conjugated structure, and high-density Lewis-base sites synergistically contribute to their excellent iodine adsorption performance. Moreover, the CMPs demonstrated good recyclability. This work provides guidance for the construction of novel iodine adsorbent materials with high efficiency in the nuclear power field.
PubMed: 38792104
DOI: 10.3390/molecules29102242 -
International Journal of Molecular... May 2024The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or LH), isoniazid (HIN or LH), or...
The interactions with calf thymus DNA (CT-DNA) of three Schiff bases formed by the condensation of hesperetin with benzohydrazide (HHSB or LH), isoniazid (HIN or LH), or thiosemicarbazide (HTSC or LH) and their Cu complexes (CuHHSB, CuHIN, and CuHTSC with the general formula [CuLH(AcO)]) were evaluated in aqueous solution both experimentally and theoretically. UV-Vis studies indicate that the ligands and complexes exhibit hypochromism, which suggests helical ordering in the DNA helix. The intrinsic binding constants () of the Cu compounds with CT-DNA, in the range (2.3-9.2) × 10, from CuHTSC to CuHHSB, were higher than other copper-based potential drugs, suggesting that π-π stacking interaction due to the presence of the aromatic rings favors the binding. Thiazole orange (TO) assays confirmed that ligands and Cu complexes displace TO from the DNA binding site, quenching the fluorescence emission. DFT calculations allow for an assessment of the equilibrium between [Cu(LH)(AcO)] and [Cu(LH)(HO)], the tautomer that binds Cu, amido (am) and not imido (im), and the coordination mode of HTSC (O, N, S), instead of (O, N, NH). The docking studies indicate that the intercalative is preferred over the minor groove binding to CT-DNA with the order [Cu(LH)(AcO)] > [Cu(LH)(AcO)] ≈ TO ≈ LH > [Cu(LH)(AcO)], in line with the experimental constants, obtained from the UV-Vis spectroscopy. Moreover, dockings predict that the binding strength of [Cu(LH)(AcO)] is larger than [Cu(LH)(HO)]. Overall, the results suggest that when different enantiomers, tautomers, and donor sets are possible for a metal complex, a computational approach should be recommended to predict the type and strength of binding to DNA and, in general, to macromolecules.
Topics: DNA; Schiff Bases; Hesperidin; Copper; Coordination Complexes; Animals; Cattle; Ligands; Molecular Docking Simulation; Isoniazid; Semicarbazides
PubMed: 38791321
DOI: 10.3390/ijms25105283 -
BMC Microbiology May 2024Cobweb disease is a fungal disease that commonly affects the cultivation and production of edible mushrooms, leading to serious yield and economic losses. It is...
BACKGROUND
Cobweb disease is a fungal disease that commonly affects the cultivation and production of edible mushrooms, leading to serious yield and economic losses. It is considered a major fungal disease in the realm of edible mushrooms. The symptoms of cobweb disease were found during the cultivation of Lyophyllum decastes. This study aimed to identify the causative pathogen of cobweb disease and evaluate effective fungicides, providing valuable insights for field control and management of L. decastes cobweb disease.
RESULTS
The causal agent of cobweb disease was isolated from samples infected and identified as Cladobotryum mycophilum based on morphological and cultural characteristics, as well as multi-locus phylogeny analysis (ITS, RPB1, RPB2, and TEF1-α). Pathogenicity tests further confirmed C. mycophilum as the responsible pathogen for this condition. Among the selected fungicides, Prochloraz-manganese chloride complex, Trifloxystrobin, tebuconazole, and Difenoconazole exhibited significant inhibitory effects on the pathogen's mycelium, with EC50 values of 0.076 µg/mL, 0.173 µg/mL, and 0.364 µg/mL, respectively. These fungicides can serve as references for future field control of cobweb disease in L. decastes.
CONCLUSION
This study is the first report of C. mycophilum as the causing agent of cobweb disease in L. decastes in China. Notably, Prochloraz-manganese chloride complex demonstrated the strongest inhibitory efficacy against C. mycophilum.
Topics: China; Fungicides, Industrial; Phylogeny; Agaricales; Ascomycota; DNA, Fungal; Triazoles; Microbial Sensitivity Tests; Strobilurins; Acetates; Dioxolanes; Imines
PubMed: 38789974
DOI: 10.1186/s12866-024-03326-0 -
The Influence of Various Crosslinking Conditions of EDC/NHS on the Properties of Fish Collagen Film.Marine Drugs Apr 2024The process of crosslinking improves the physicochemical properties of biopolymer-based composites, making them valuable for biomedical applications. EDC/NHS-crosslinked...
The process of crosslinking improves the physicochemical properties of biopolymer-based composites, making them valuable for biomedical applications. EDC/NHS-crosslinked collagen materials have a significant potential for tissue engineering applications, due to their enhanced properties and biocompatibility. Chemical crosslinking of samples can be carried out in several ways, which is crucial and has a direct effect on the final properties of the obtained material. In this study, the effect of crosslinking conditions on the properties of collagen films using EDC and NHS was investigated. Studies included FTIR spectroscopy, AFM, swelling and degradation tests, mechanical testing and contact angle measurements. Evaluation of prepared collagen films indicated that both crosslinking agents and crosslinking conditions influenced film properties. Notable alternations were observed in the infrared spectrum of the sample, to which EDC was added directly to the fish collagen solution. The same sample indicated the lowest Young modulus, tensile strength and breaking force parameters and the highest elongation at break. All samples reached the maximum swelling degree two hours after immersion in PBS solution; however, the immersion-crosslinked samples exhibited a significantly lower degree of swelling and were highly durable. The highest roughness was observed for the collagen film crosslinked with EDC, whereas the lowest was observed for the specimen crosslinked with EDC with NHS addition. The crosslinking agents increased the surface roughness of the collagen film, except for the sample modified with the addition of EDC and NHS mixture. All films were characterized by hydrophilic character. The films' modification resulted in a decrease in their hydrophilicity and wettability. Our research allows for a comparison of proposed EDC/NHS crosslinking conditions and their influence on the physicochemical properties of fish collagen thin films. EDC and NHS are promising crosslinking agents for the modification of fish collagen used in biomedical applications.
Topics: Animals; Cross-Linking Reagents; Collagen; Fishes; Biocompatible Materials; Tensile Strength; Tissue Engineering; Spectroscopy, Fourier Transform Infrared; Materials Testing; Carbodiimides
PubMed: 38786585
DOI: 10.3390/md22050194 -
Biomolecules Apr 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly targets the upper respiratory tract. It gains entry by interacting with the host cell receptor...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly targets the upper respiratory tract. It gains entry by interacting with the host cell receptor angiotensin-converting enzyme 2 (ACE2) via its heavily glycosylated spike glycoprotein. SARS-CoV-2 can also affect the gastrointestinal tract. Given the significant role of glycosylation in the life cycle of proteins and the multisystem target of SARS-CoV-2, the role of glycosylation in the interaction of S1 with ACE2 in Caco-2 cells was investigated after modulation of their glycosylation patterns using -butyldeoxynojirimycin (NB-DNJ) and 1-deoxymannojirimycin (dMM), in addition to mutant CHO cells harboring mutations at different stages of glycosylation. The data show a substantial reduction in the interactions between the altered glycosylation forms of S1 and ACE2 in the presence of NB-DNJ, while varied outcomes resulted from dMM treatment. These results highlight the promising effects of NB-DNJ and its potential use as an off-label drug to treat SARS-CoV-2 infections.
Topics: Humans; Caco-2 Cells; Angiotensin-Converting Enzyme 2; Glycosylation; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Animals; CHO Cells; Cricetulus; Protein Transport; COVID-19; 1-Deoxynojirimycin; Protein Binding; Intestinal Mucosa
PubMed: 38785944
DOI: 10.3390/biom14050537 -
Biomolecules Apr 2024The problem of antimicrobial resistance is becoming a daunting challenge for human society and healthcare systems around the world. Hence, there is a constant need to...
The problem of antimicrobial resistance is becoming a daunting challenge for human society and healthcare systems around the world. Hence, there is a constant need to develop new antibiotics to fight resistant bacteria, among other important social and economic measures. In this regard, murepavadin is a cyclic antibacterial peptide in development. The synthesis of murepavadin was undertaken in order to optimize the preparative protocol and scale-up, in particular, the use of new activation reagents. In our hands, classical approaches using carbodiimide/hydroxybenzotriazole rendered low yields. The use of novel carbodiimide and reagents based on OxymaPure and Oxy-B is discussed together with the proper use of chromatographic conditions for the adequate characterization of peptide crudes. Higher yields and purities were obtained. Finally, the antimicrobial activity of different synthetic batches was tested in three strains, including highly resistant ones. All murepavadin batches yielded the same highly active MIC values and proved that the chiral integrity of the molecule was preserved throughout the whole synthetic procedure.
Topics: Pseudomonas aeruginosa; Microbial Sensitivity Tests; Peptides, Cyclic; Anti-Bacterial Agents; Antimicrobial Peptides; Carbodiimides; Humans
PubMed: 38785933
DOI: 10.3390/biom14050526 -
Chemical Science May 2024The synthesis and scale-up of high quality covalent organic frameworks (COFs) remains a challenge due to slow kinetics of the reversible bond formation and the need for...
The synthesis and scale-up of high quality covalent organic frameworks (COFs) remains a challenge due to slow kinetics of the reversible bond formation and the need for precise control of reaction conditions. Here we report the rapid synthesis of faceted single crystals of two-dimensional (2D) COFs using a continuous flow reaction process. Two imine linked materials were polymerized to the hexagonal CF-TAPB-DMPDA and the rhombic CF-TAPPy-PDA COF, respectively. The reaction conditions were optimized to produce single crystals of micrometer size, which notably formed when the reaction was cooling to room temperature. This indicated a growth mechanism consistent with the fusion of smaller COF particles. The optimized conditions were used to demonstrate the scalability of the continuous approach by synthesizing high quality, faceted COFs at a rate of more than 1 g h. The materials showed high crystallinity and porosity with surface areas exceeding 2000 m g. Additionally, the versatility of the continuous flow reaction approach was demonstrated on a post-synthetic single crystal to single crystal demethylation of CF-TAPB-DMPDA to afford a hydroxyl functionalized COF CF-TAPB-DHPDA. Throughout the modification process, the material maintained its hexagonal morphology, crystallinity, and porosity. This work reports the first example of synthesizing and post-synthetically modifying imine linked COF single crystals in continuous flow and will prove a first step towards scaling high quality COFs to industrial levels.
PubMed: 38784733
DOI: 10.1039/d4sc01128g