An Integrated Polysaccharide Hydrogel with Versatile Fluorescence Responses through Noncovalent Reformation of Gel Aggregation and for Bioimaging.

Functionalized hydrogels, with their unique and adaptable structures, have attracted significant attention in materials and biomaterials research. Fluorescent hydrogels are particularly noteworthy for their sensing capabilities and ability to mimic cellular matrices, facilitating cell infiltration and tracking of drug delivery. Structural elucidation of hydrogels is crucial for understanding their responses to stimuli such as the pH, temperature, and solvents. This study developed a fluorescent hydrogel by functionalizing chitosan with p-cresol-based quinazolinone aldehyde. Confocal microscopy revealed the hydrogel's intriguing fluorogenic properties. The hydrogel exhibited enhanced fluorescence and a tunable network morphology, influenced by the THF-water ratio. The study investigated the control of gel network reformation in different media and analyzed the fluorescence responses and structural changes of the sugar backbone and fluorophore. Proper selection of mixed solvents is essential for optimizing the hydrogel as a fluorescence probe for bioimaging. This hydrogel demonstrated greater swelling properties, making it highly suitable for drug delivery applications.

In silico investigation on the separation of disulfide bonds by N-heterocyclic carbene.

Herein, the separation of a disulfide bond using different nucleophilic agents like tri-methyl phosphine (TMP), tris (2-carboxyethyl) phosphine (TCEP), and N-heterocyclic carbene (NHC) has been investigated. Both TMP and TCEP have demonstrated their ability to break disulfide bonds through the SN2 mechanism. However, it is worth noting that these reactions are endothermic. While searching for a suitable nucleophile, it was observed that the NHC-mediated reaction was exothermic. The natural bond orbital (NBO), principal interacting orbital (PIO) and extended transition state-natural orbitals for chemical valence (ETS-NOCV) studies help understand the electron transfer process between interacting orbitals during the chemical reactions.

Anti-MRSA activity of chlorophenyl pyrrolo benzodiazepines compound.

Antibiotic resistant is the major concern in public health to control the infectious diseases. MRSA (Methicillin-resistant Staphylococcus aureus) is a significant concern in healthcare settings due to its resistance to many antibiotics, including methicillin and other beta-lactams. MRSA infection difficult to treat and increases the risk of complications. Here, we have tested a series of highly condensed heterocyclic derivatives of pyrrolo[1,2-a][1,4]benzodiazepines. Compounds were tested against both, Gram-positive bacteria, Staphylococcus aureus and S. epidermidis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to assess the antimicrobial efficacy. Compared to Gram-negative bacteria, compounds showed much stronger antibacterial activity against Gram-positive bacteria. SM-5 [Ethyl2-(7-(4-chlorophenyl)-4-methoxy-6,7,8,13-tetrahydro-5H-benzo[e]benzo[5,6][1,4]diazepino[2,1-a]isoindol-15-yl)acetate] derivative was selected as best on the basis of higher therapeutic index among the tested compounds, showed MIC value of 7.81 µg. ml-1 against Staphylococcus strains. Molecular docking analysis between cell wall biosynthesis protein of S. aureus and SM-5 revealed that PBP2a showed the highest binding energy (-8.3 Kcal mol-1), followed by beta-lactam-inducible PBP4 (-7.7 Kcal mol-1), and lipoteichoic acid synthase (-7.5 Kcal mol-1) which is comparably higher than methicillin. Ground state energy calculations by DFT analysis revealed that compound SM-5 and SM-6, almost have equal electronegativity 0.11018 au which also satisfy the quality of the compound reactivity. Analysis of their biofilm inhibition in vitro and in silico toxicity analysis demonstrated their substantial potential to be a kind of future lead antibiotic.

Combined in†vitro/in silico approaches, molecular dynamics simulations and safety assessment of the multifunctional properties of thymol and carvacrol: A comparative insight.

Bioactive compounds derived from medicinal plants have acquired immense attentiveness in drug discovery and development. The present study investigated in vitro and predicted in silico the antibacterial, antifungal, and antiviral properties of thymol and carvacrol, and assessed their safety. The performed microbiological assays against Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica Typhimurium revealed that the minimal inhibitory concentration values ranged from (0.078 to 0.312 mg/mL) and the minimal fungicidal concentration against Candida albicans was 0.625 mg/mL. Molecular docking simulations, stipulated that these compounds could inhibit bacterial replication and transcription functions by targeting DNA and RNA polymerases receptors with docking scores varying between (-5.1 to -6.9 kcal/mol). Studied hydroxylated monoterpenes could hinder C. albicans growth by impeding lanosterol 14α-demethylase enzyme and showed a (ΔG=-6.2 and -6.3 kcal/mol). Computational studies revealed that thymol and carvacrol could target the SARS-Cov-2 spike protein of the Omicron variant RBD domain. Molecular dynamics simulations disclosed that these compounds have a stable dynamic behavior over 100 ns as compared to remdesivir. Chemo-computational toxicity prediction using Protox II webserver indicated that thymol and carvacrol could be safely and effectively used as drug candidates to tackle bacterial, fungal, and viral infections as compared to chemical medication.

In Silico Identification of a Potent Arsenic Based Approved Drug Darinaparsin against SARS-CoV-2: Inhibitor of RNA Dependent RNA polymerase (RdRp) and Essential Proteases.

BACKGROUND: COVID-19 is a life-threatening novel corona viral infection to our civilization and spreading rapidly. Tremendousefforts have been made by the researchers to search for a drug to control SARS-CoV-2. METHODS: Here, a series of arsenical derivatives were optimized and analyzed with in silico study to search the inhibitor of RNA dependent RNA polymerase (RdRp), the major replication factor of SARS-CoV-2. All the optimized derivatives were blindly docked with RdRp of SARS-CoV-2 using iGEMDOCK v2.1. RESULTS: Based on the lower idock score in the catalytic pocket of RdRp, darinaparsin (-82.52 kcal/- mol) was revealed to be the most effective among them. Darinaparsin strongly binds with both Nsp9 replicase protein (-8.77 kcal/mol) and Nsp15 endoribonuclease (-8.3 kcal/mol) of SARS-- CoV-2 as confirmed from the AutoDock analysis. During infection, the ssRNA of SARS-CoV-2 is translated into large polyproteins forming viral replication complex by specific proteases like 3CL protease and papain protease. This is also another target to control the virus infection where darinaparsin also performs the inhibitory role to proteases of 3CL protease (-7.69 kcal/mol) and papain protease (-8.43 kcal/mol). CONCLUSION: In the host cell, the furin protease serves as a gateway to the viral entry and darinaparsin docked with furin protease, which revealed a strong binding affinity. Thus, screening of potential arsenic drugs would help in providing the fast in-vitro to in-vivo analysis towards the development of therapeutics against SARS-CoV-2.

Theoretical analysis of bacterial efflux pumps inhibitors: Strategies in-search of competent molecules and develop next.

Multi-drug resistance (MDR) bacteria pose a significant threat to our ability to effectively treat infections due to the development of several antibiotic resistant mechanisms. A major component in the development of the MDR phenotype in MDR bacteria is over expression of different-type of efflux pumps, which actively pump out antibacterial agents and biocides from the periplasm to the outside of the cell. Consequently, bacterial efflux pumps are an important target for developing novel antibacterial treatments. Potent efflux pump inhibitors (EPIs) could be used as adjunctive therapies that would increase the potency of existing antibiotics and decrease the emergence of MDR bacteria. Several potent inhibitors of efflux pumps have been reported which has been summarized here. All the natural and synthetic EPIs were optimized with Gaussian and Avogadro software. The optimized structures were docked with each class of efflux pumps and their bonding parameters were computed. The theoretical analyses were performed with density functional theory (DFT). Overall, computational study revealed a good trend of electrophilicity and ionization potential of the EPIs, the obtained average values are within in the range of 0.001414 AU ± 0.00032 and 0.208821 AU ± 0.015545, respectively. Interestingly, cathinone interacts with most of the efflux pumps among the tested inhibitors. The electrophilicity and ionization potential of cathinone are 0.00198 and 0.2388 AU, respectively. The study opens a new road for designing future-generation target-specific efflux pump inhibitors, as well as one molecule with multiple inhibition abilities.

Synthesis, characterization and nucleic acid binding studies of mononuclear copper(II) complexes derived from azo containing O, O donor ligands.

Azo linked salicyldehyde and a new 2-hydroxy acetophenone based ligands (HL1 and HL2) with their copper(II) complexes [Cu(L1)2] (1) and [Cu(L2)2] (2) were synthesized and characterized by spectroscopic methods such as 1H, 13C NMR, UV-Vis spectroscopy and elemental analyses. Calculation based on Density Functional Theory (DFT), have been performed to obtain optimized structures. Binding studies of these copper (II) complexes with calf thymus DNA (ct-DNA) and torula yeast RNA (t-RNA) were analyzed by absorption spectra, emission spectra and Viscosity studies and Molecular Docking techniques. The absorption spectral study indicated that the copper(II) complexes of 1 and 2 had intrinsic binding constants with DNA or RNA in the range of 7.6 ± 0.2 × 103 M-1 or 6.5 ± 0.3 × 103M-1 and 5.7 ± 0.4 × 104 M-1 or 1.8 ± 0.5 × 103 M-1 respectively. The synthesized compounds and nucleic acids were simulated by molecular docking to explore more details mode of interaction of the complexes and their orientations in the active site of the receptor.

On the making of aromatic organometallic superalkali complexes.

Superalkalis are complexes that have a lower ionization energy than that of the corresponding alkali and alkaline earth metals. Based on First Principles calculations, the plausible existence of a superalkali complex consisting of an all-metal aromatic trigonal Au3 core coupled with pyridine (Py) and imidazole (IMD) ligands is suggested. The calculated ionization energy (IE) values of the subsequent organometallic complexes, Au3(Py)3 and Au3(IMD)3, are low, thereby mimicking the usual behavior of a superalkali. First order hyperpolarizability calculations show the existence of non-linear optical properties in some of the complexes, which is also on par with the properties of a superalkali.

N, N'-Olefin functionalized bis-imidazolium gold(I) salt is an efficient candidate to control keratitis-associated eye infection.

Keratitis treatment has become more complicated due to the emergence of bacterial or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical applications of N-heterocyclic carbene complexes have received remarkable attention due to their antimicrobial properties. In this paper, the new precursor, 3,3'-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore, silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2; 2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their corresponding ligands. All compounds were screened for their antimicrobial activities against multiple keratitis-associated human eye pathogens, including bacteria and fungi. Complexes 2a and 3a showed highest activity, and the effectiveness of 3a was also studied, focusing eradication of pathogen biofilm. Furthermore, the structures of 1a, 2a and 3b were determined using single crystal X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action of 3a was evaluated by scanning electron microscopy and docking experiments, suggesting that its target is the cell membrane. In summary, 3a may be helpful in developing antimicrobial therapies in patients suffering from keratitis-associated eye infections caused by multidrug-resistant pathogens.