Comparing the crystal structures and spectroscopic properties of a p-hydroxy styrylquinolinium dye with those of its p-dimethylamino analogue.

Two previously synthesized styrylquinolinium dyes, namely (E)-1-butyl-4-(4-(dimethylamino)styryl)quinolinium iodide (D36) and (E)-1-butyl-4-(4-hydroxystyryl)quinolinium iodide (D34), were compared in terms of their properties by single-crystal X-ray diffraction (XRD), Hirshfeld surface analysis, Fourier transform Raman (FT-Raman), Fourier transform infrared (FT-IR), fluorescence, and ultraviolet-visible (UV-Vis) spectroscopy, and 1H- and 13C-NMR methods. Both dyes D36 and D34 crystallized in the triclinic and monoclinic systems in the centrosymmetric space groups P-1 and P21/n, respectively. The unit cell of D36 contains two molecules of the dye, participating in weak intermolecular interactions, whereas that of D34 contains four formula units. The phenolic hydroxy group of D34 participates in the formation of a hydrogen bond with the iodide anion. The 4-styrylquinolinium moieties of the cationic dye molecules are nearly planar. The dihedral angle between the mean planes through the ten-membered quinolinium system and the benzene ring is 7.5° in D36 and 5.9(1)° in D34. The structural parameters planarity and bond length alternation (BLA) are discussed, which are important for the evaluation of the first hyperpolarizability ß at the molecular level, even in a centrosymmetric crystal. The UV-visible spectra of the dyes in 14 solvents of different polarities were investigated. The reversible solvatochromic behavior of the dyes is demonstrated experimentally and compared with known "binuclear dyes" by evaluating the Rezende model. Dye D36 does not fluoresce, and D34 has a very low emission in the solvents tested.

Novel Anthranilic Acid Hybrids-An Alternative Weapon against Inflammatory Diseases.

Anti-inflammatory drugs are used to relieve pain, fever, and inflammation while protecting the cardiovascular system. However, the side effects of currently available medications have limited their usage. Due to these adverse effects, there is a significant need for new drugs. The current trend of research has shifted towards the synthesis of novel anthranilic acid hybrids as anti-inflammatory agents. Phenyl- or benzyl-substituted hybrids exerted very good anti-inflammatory effects in preventing albumin denaturation. To confirm their anti-inflammatory effects, additional ex vivo tests were conducted. These immunohistochemical studies explicated the same compounds with better anti-inflammatory potential. To determine the binding affinity and interaction mode, as well as to explain the anti-inflammatory activities, the molecular docking simulation of the compounds was investigated against human serum albumin. The biological evaluation of the compounds was completed, assessing their antimicrobial activity and spasmolytic effect. Based on the experimental data, we can conclude that a collection of novel hybrids was successfully synthesized, and they can be considered anti-inflammatory drug candidates-alternatives to current therapeutics.

Synthesis, Molecular Docking, and Biological Evaluation of Novel Anthranilic Acid Hybrid and Its Diamides as Antispasmodics.

The present article focuses on the synthesis and biological evaluation of a novel anthranilic acid hybrid and its diamides as antispasmodics. Methods: Due to the predicted in silico methods spasmolytic activity, we synthesized a hybrid molecule of anthranilic acid and 2-(3-chlorophenyl)ethylamine. The obtained hybrid was then applied in acylation with different acyl chlorides. Using in silico analysis, pharmacodynamic profiles of the compounds were predicted. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial, cytotoxic, anti-inflammatory activity, and ex vivo spasmolytic activity. Density functional theory (DFT) calculation, including geometry optimization, molecular electrostatic potential (MEP) surface, and HOMO-LUMO analysis for the synthesized compounds was conducted using the B3LYP/6-311G(d,p) method to explore the electronic behavior, reactive regions, and stability and chemical reactivity of the compounds. Furthermore, molecular docking simulation along with viscosity measurement indicated that the newly synthesized compounds interact with DNA via groove binding mode. The obtained results from all the experiments demonstrate that the hybrid molecule and its diamides inherit spasmolytic, antimicrobial, and anti-inflammatory capabilities, making them excellent candidates for future medications.

Experimental and theoretical study of the cytosine tautomerism through excited states.

CONTEXT: The irradiation of water solution of cytosine with UV light (λmax = 254 nm) shows oxo-hydroxy tautomerism with a rate constant of 6.297 × 10-3 min-1. The order of the reaction implies a tautomeric conversion. After removing the UV light source, we observed a dark reaction with a rate constant of 1.473 × 10-3 min-1 which leads to a restoration of the initial tautomer as before the irradiation. The mechanism of oxo-hydroxy tautomerism of cytosine in water solution was studied in the excited state. It was found that the transformations occur along the 1πσ* excited-state reaction paths which link the Franck-Condon geometries of the tautomers and the conical intersections S0/S1 connected with the H-detachment processes of the corresponding bonds. Furthermore, we established that the conical intersections S0/S1 are also mutually accessible along the 1πσ* excited-state reaction paths. METHODS: The ground-state equilibrium geometries were optimized at the B3LYP/aug-cc-pVDZ level of theory in water environment according to PCM as well as at the CC2/aug-cc-pVDZ level in the gas phase. The TD B3LYP and CC2 methods were applied for the study of the excited states. The tautomerization mechanisms were studied with the use of the linear interpolation in internal coordinates approach using the optimized geometries of tautomers minima and conical intersections S0/S1 at the CASSCF(6,6)/6-31G* level. All calculations were performed with the GAUSSIAN 16 commercial software.

Drug-Delivery Silver Nanoparticles: A New Perspective for Phenindione as an Anticoagulant.

Anticoagulants prevent the blood from developing the coagulation process, which is the primary cause of death in thromboembolic illnesses. Phenindione (PID) is a well-known anticoagulant that is rarely employed because it totally prevents coagulation, which can be a life-threatening complication. The goal of the current study is to synthesize drug-loaded Ag NPs to slow down the coagulation process. Methods: A rapid synthesis and stabilization of silver nanoparticles as drug-delivery systems for phenindione (PID) were applied for the first time. Results: Several methods are used to determine the size of the resulting Ag NPs. Additionally, the drug-release capabilities of Ag NPs were established. Density functional theory (DFT) calculations were performed for the first time to indicate the nature of the interaction between PID and nanostructures. DFT findings supported that galactose-loaded nanostructure could be a proper delivery system for phenindione. The drug-loaded Ag NPs were characterized in vitro for their antimicrobial, cytotoxic, and anticoagulant activities, and ex vivo for spasmolytic activity. The obtained data confirmed the drug-release experiments. Drug-loaded Ag NPs showed that prothrombin time (PT, sec) and activated partial thromboplastin time (APTT, sec) are approximately 1.5 times longer than the normal values, while PID itself stopped coagulation at all. This can make the PID-loaded Ag NPs better therapeutic anticoagulants. PID was compared to PID-loaded Ag NPs in antimicrobial, spasmolytic activity, and cytotoxicity. All the experiments confirmed the drug-release results.

Antiviral Potential of Specially Selected Bulgarian Propolis Extracts: In Vitro Activity against Structurally Different Viruses.

Propolis is a natural mixture of resins, wax, and pollen from plant buds and flowers, enriched with enzymes and bee saliva. It also contains various essential oils, vitamins, mineral salts, trace elements, hormones, and ferments. It has been found that propolis possesses antimicrobial, antiviral, and anti-inflammatory properties. We have studied the antiviral activity of six extracts of Bulgarian propolis collected from six districts of Bulgaria. The study was conducted against structurally different viruses: human coronavirus strain OC-43 (HCoV OC-43) and human respiratory syncytial virus type 2 (HRSV-2) (enveloped RNA viruses), human herpes simplex virus type 1 (HSV-1) (enveloped DNA virus), human rhinovirus type 14 (HRV-14) (non-enveloped RNA virus) and human adenovirus type 5 (HadV-5) (non-enveloped DNA virus). The influence of the extracts on the internal replicative cycle of viruses was determined using the cytopathic effect (CPE) inhibition test. The virucidal activity, its impact on the stage of viral adsorption to the host cell, and its protective effect on healthy cells were evaluated using the final dilution method, making them the focal points of interest. The change in viral infectivity under the action of propolis extracts was compared with untreated controls, and Δlgs were determined. Most propolis samples administered during the viral replicative cycle demonstrated the strongest activity against HCoV OC-43 replication. The influence of propolis extracts on the viability of extracellular virions was expressed to a different degree in the various viruses studied, and the effect was significantly stronger in those with an envelope. Almost all extracts significantly inhibited the adsorption step of the herpes virus and, to a less extent, of the coronavirus to the host cell, and some of them applied before viral infection demonstrated a protective effect on healthy cells. Our results enlarge the knowledge about the action of propolis and could open new perspectives for its application in viral infection treatment.

Drug-Loaded Silver Nanoparticles-A Tool for Delivery of a Mebeverine Precursor in Inflammatory Bowel Diseases Treatment.

Chronic, multifactorial illnesses of the gastrointestinal tract include inflammatory bowel diseases. One of the greatest methods for regulated medicine administration in a particular region of inflammation is the nanoparticle system. Silver nanoparticles (Ag NPs) have been utilized as drug delivery systems in the pharmaceutical industry. The goal of the current study is to synthesize drug-loaded Ag NPs using a previously described 3-methyl-1-phenylbutan-2-amine, as a mebeverine precursor (MP). Methods: A green, galactose-assisted method for the rapid synthesis and stabilization of Ag NPs as a drug-delivery system is presented. Galactose was used as a reducing and capping agent forming a thin layer encasing the nanoparticles. Results: The structure, size distribution, zeta potential, surface charge, and the role of the capping agent of drug-loaded Ag NPs were discussed. The drug release of the MP-loaded Ag NPs was also investigated. The Ag NPs indicated a very good drug release between 80 and 85%. Based on the preliminary results, Ag NPs might be a promising medication delivery system for MP and a useful treatment option for inflammatory bowel disease. Therefore, future research into the potential medical applications of the produced Ag NPs is necessary.

In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors.

Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. METHODS: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. RESULTS: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca2+ channel regulation, Ca2+ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. CONCLUSION: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS.

Synthesis, crystal structure, and spectroscopic properties of new stilbazolium salt with enlarged π-conjugated system.

A new stilbazolium dye 4-{(E)-2-[4-(dimethylamino)naphthalen-1-yl]ethenyl}-1-methylquinolinium iodide monohydrate (DANSQI) having enlarged π-conjugated system was synthesized and characterized by X-ray diffraction, IR, Raman, UV-Vis, Fluorescence, (1)H- and (13)C NMR spectroscopy. Quantum chemical calculations were performed to obtain electronic structure and vibrational data, using DFT. The crystals are monoclinic, space group P21/n, with a=8.0751(14), b=25.839(4), c=10.9031(15) Å, V=2141.4(6) Å(3), and Z=4 (at 300(2) K). The unit cell contains four molecules of the dye, participating in weak intermolecular interactions. The cation is nearly flat with a deviation of the planarity of 5.08 (1)°. The dye investigated is the first stilbazolium iodide containing water molecule in the solid state therefore the N-dimethylamino group declines significantly from planarity, as indicated by C13N1C2C3 torsion angle of 16.08°. The dye studied shows solvatochromism of 84 nm in visible region and very large Stokes shift up to 253 nm. The intensity of fluorescence bands strongly depends on solvent polarity.