Synthesis, cytotoxicity, anti-inflammatory, anti-metastatic and anti-oxidant activities of novel chalcones incorporating 2-phenoxy-N-arylacetamide and thiophene moieties: induction of apoptosis in MCF7 and HEP2 cells.

Eight Novel chalcones were synthesized and their structures were confirmed by different spectral tools. All the prepared compounds were subjected to SRB cytotoxic screening against several cancer cell lines. Compound 5c exerted the most promising effect against MCF7 and HEP2 cells with IC50 values of 9.5 and 12 µg/mL, respectively. Real-time PCR demonstrated the inhibitory effect of compound 5c on the expression level of Antigen kiel 67 (KI-67), Survivin, Interleukin-1beta (IL-1B), Interleukin-6 (IL-6), Cyclooxygenase-2 (COX-2) and Protein kinase B (AKT1) genes. Flow-cytometric analysis of the cell cycle indicated that compound 5c stopped the cell cycle at the G0/G1 and G2/M phases in MCF7 and HEP2 treated cells, respectively. ELISA assay showed that Caspase 8, Caspase 9, P53, BAX, and Glutathione (GSH) were extremely activated and Matrix metalloproteinase 2 (MMP2), Matrix metalloproteinase 9 (MMP9), BCL2, Malondialdehyde (MDA), and IL-6 were deactivated in 5c treated MCF7 and HEP2 cells. Wound healing revealed that chalcone 5c reduced the ability to close the scrape wound and decreased the number of migrating MCF7 and HEP2 cells compared to the untreated cells after 48 h. Theoretical molecular modeling against P53 cancer mutant Y220C and Bcl2 showed binding energies of -22.8 and -24.2 Kcal/mole, respectively, which confirmed our ELISA results.

Novel hybrid thiazoles, bis-thiazoles linked to azo-sulfamethoxazole: Synthesis, docking, and antimicrobial activity.

The reaction of sulfamethoxazolehydrazonoyl chloride with thiosemicarbazones, bis-thiosemicarbazones, or 4-amino-3-mercapto-1,2,4-triazole in dioxane in the presence of triethylamine as a basic catalyst at reflux resulted in the regioselective synthesis of thiazoles and bis-thiazoles linked to azo-sulfamethoxazole as novel hybrid molecules. The structures of the new compounds were confirmed using a range of spectra. Each compound's antibacterial properties were evaluated using the agar well-diffusion technique, and most of them demonstrated significant potency. In silico investigations revealed that the described compounds had strong interactions with the binding sites of MurE ligase, tyrosyl-tRNA synthetase, and dihydropteroate synthase, demonstrating inhibitory activity.

Utility of 2-Chloro-N-arylacetamide and 1,1'-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines].

A series of novel thieno[2,3-b]pyridines linked to N-aryl carboxamides or (carbonylphenoxy)-N-(aryl)acetamides, as well as bis(thieno[2,3-b]pyridines) linked to piperazine core via methanone or carbonylphenoxyethanone units, were synthesized by treating the appropriate chloroacetyl- or bis-bromoacetyl derivatives with 2-mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. The spectral data were used to determine the compositions of novel compounds.

Novel Bis(2-cyanoacrylamide) Linked to Sulphamethoxazole: Synthesis, DNA Interaction, Anticancer, ADMET, Molecular Docking, and DFT Studies.

In the light of advancement and potential extensive use of medication design and therapy, new bis(cyanoacrylamides) incorporating sulphamethoxazole derivatives (7 a-7 f) were synthesized and confirmed by different spectral tools. In vitro anticancer activity towards different human cancer cells (HCT116, MDA-MB-231 and A549) was assessed using MTT assay. Among all derivatives, 4C- and 6C-spacer derivatives (7 e and 7 f) had the most potent growth inhibitory activities against HCT116 cells with IC50 values of 39.7 and 28.5 µM, respectively. 7 e and 7 f induced apoptosis and suppressed migration of HCT116 cells. These compounds also induced a significant increase in caspase-3 and CDH1 activities, and a downregulation of Bcl2 using ELISA. pBR322 DNA cleavage activities of cyanoacrylamides were determined using agarose gel electrophoresis. Furthermore, 7 e and 7 f showed good DNA and BSA binding affinities using different spectroscopic techniques. Furthermore, molecular docking for 7 e and 7 f was performed to anticipate their binding capabilities toward various proteins (Bcl2, CDH1 and BSA). The docking results were well correlated with those of experimental results. Additionally, density functional theory and ADMET study were performed to evaluate the molecular and pharmacokinetic features of 7 e and 7 f, respectively. Thus, this work reveals promising antitumor lead compounds that merit future research and activity enhancement.

Synthesis of Novel Diphenyl Ether-Based Bis-Heterocycles as Novel Hybrid Molecules via Michael and Other Cyclocondensation Reactions.

Molecular hybridization is a technique used in drug creation that involves combining the pharmacophoric moieties of multiple bioactive compounds to create a new hybrid molecule with better affinity and effectiveness. In this regard, we created unique hybrid molecules out of diphenyl ether-linked fused pyrans and other heterocycles. The Michael reaction of 4,4'-oxydibenzaldehyde with malononitrile and various active methylene derivatives, as well as enaminone derivatives, produced the matching bis-fused pyrans and fused pyridines, both connected to a diphenyl ether moiety. Furthermore, the acid-catalyzed reaction of 4,4'-oxydibenzaldehyde with dimedone or ß-naphthol produced the corresponding new bis(hexahydro-1H-xanthene-1,8-dione) and bis(14H-dibenzo[a,j]xanthene). The processes by which the target products are formed were also examined.

Effectiveness of full Pulpotomy compared with Root canal treatment in managing teeth with signs and symptOms indicative of irreversible pulpitis: a protocol for prospectiVE meta-analysis of individual participant data of linked randomised clinical trials (PROVE).

BACKGROUND: Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment. METHODS: Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists. RESULTS: The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023. DISCUSSION: PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development. TRIAL REGISTRATION: PROSPERO CRD42023446809. Registered on 08 February 2023.

Novel Scaffolds Based on Bis-thiazole Connected to Quinoxaline or Thienothiophene through 2-Phenoxy-N-arylacetamide Groups as New Hybrid Molecules: Synthesis, Antibacterial Activity, and Molecular Docking Investigations.

The resistance of microorganisms to antimicrobials has endangered the health of many people across the world. Overcoming the resistance problem will require the invention of molecules with a new mechanism of action so that no cross-resistance with existing therapies occurs. Because of their powerful antibacterial activity against a wide spectrum of Gram-positive and Gram-negative bacterial strains, heterocyclic compounds are appealing candidates for medicinal chemists. In this regard, as unique hybrid compounds, we synthesized a novel family of bis-thiazoles linked to quinoxaline or thienothiophene via the 2-phenoxy-N-arylacetamide moiety. The target compounds were synthesized by reacting the relevant bis(α-haloketones) with the corresponding thiosemicarbazones in EtOH at reflux with a few drops of TEA. Under comparable reaction conditions, the isomeric bis(thiazoles) were synthesized by reacting the appropriate bis(thiosemicarbazone) with the respective α-haloketones. The structures of the novel compounds were confirmed using elements and spectral data. All of the synthesized compounds were tested for antibacterial activity in vitro. With an inhibitory zone width of 12 mm, compound 12a had the same activity as the reference medication tobramycin against Staphylococcus aureus. Compound 12b showed 20 mg/mL as a minimum inhibitory concentration (MIC) against Bacillus subtilis. Some of the synthesized compounds were tested via molecular docking against two bacterial proteins (dihydrofolate reductase and tyrosyl-tRNA synthetase).

Changes in morphological traits, anatomical and molecular alterations caused by gamma-rays and zinc oxide nanoparticles in spinach (Spinacia oleracea L.) plant.

Spinach seeds were irradiated with gamma-rays after that soaked in zinc oxide nanoparticles (ZnO-NPs) at 0.0, 50, 100 and 200 ppm for twenty-four hours at room temperature. Vegetative plant growth, photosynthetic pigments, and proline contents were investigated. Also, anatomical studies and the polymorphism by the SCoT technique were conducted. The present results revealed that the germination percentage was at the maximum values for the treatment of 100 ppm ZnO-NPs (92%), followed by 100 ppm ZnO-NPs + 60 Gy (90%). The application of ZnO-NPs resulted in an enhancement in the plant length. The maximum of chlorophylls and carotenoids content was recorded in the treatment, 100 ppm ZnO-NPs + 60 Gy. Meanwhile, the irradiation dose level (60 Gy) with all ZnO-NPs treatments increased proline content and reached its maximum increase to 1.069 mg/g FW for the treatment 60 Gy combined with 200 ppm ZnO-NPs. Also, the anatomical studies declared that there were variations between the treatments; un-irradiated and irradiated combined with ZnO-NPs plants which reveal that the leave epidermal tissue increased with 200 ppm ZnO-NPs in both the upper and lower epidermis. While irradiated plants with 60 Gy combined with 100 ppm ZnO-NPs gave more thickness of upper epidermis. As well as SCoT molecular marker technique effectively induced molecular alterations between the treatments. Where, SCoT primers targeted many new and missing amplicons that are expected to be associated with the lowly and highly expressed genes with 18.2 and 81.8%, respectively. Also, showed that the soaking in ZnO-NPs was helped for reducing molecular alteration rate, both spontaneous and induced by gamma irradiation. This nominates ZnO-NPs as potential nano-protective agents that can reduce irradiation-induced genetic damage.

Experimental and theoretical studies of linear and non-linear optical properties of novel fused-triazine derivatives for advanced technological applications.

Controlling photophysical properties is critical for the continued development of electroluminescent devices and luminescent materials. The preparation and study of novel molecules suitable as luminescent for the development of optoelectrical devices have recently received a lot of attention. Even though the as-triazine unit is a good building block for organic active substances, it is rarely used in this context. We created here novel bis-triazine derivative dyes in the far UV-Vis range by alkylation of triazine-thione derivatives with appropriate dibromo compounds. At the B3LYP/6-311**G(d,p) basis set, their optimal molecular structures were obtained. DFT technique confirmed that the new triazine derivatives are in noncoplanar with one of the two phenyl rings and the triazine plane rotating out by 102.09. Also, depending on the energy gap difference between HOMO and LUMO, some important parameters including chemical potential (π), electronegativity (χ), and chemical hardness (η) were calculated. The compounds may be readily polarized and have significant NLO characteristics, as seen by the tiny HOMO-LUMO energy gap. The calculated values for the polarizability (α) of the two new triazine derivatives have the range 6.09-10.75 × 10-24 (esu). The emission peaks seemed to move to the long-wavelength (redshift), with a rise in the fluorescence band, suggesting that the singlet excited state is more polar than the ground state. The influence of solvent polarity and the intermolecular charge transfer (ICT) processes are reflected in the photophysical properties of new fused triazine derivatives. These properties such as extinction coefficient, absorption and emission cross-sections, fluorescence quantum yield, fluorescence lifetime, oscillator strength, the dipole moment, radiative decay rate constant, the energy yield of fluorescence, and the attenuation length were assessed and discussed.

Hantzsch-Like Synthesis, DNA Photocleavage, DNA/BSA Binding, and Molecular Docking Studies of Bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) Analogs Linked to Naphthalene Core.

The cyclocondensation reaction of aldehydes with dimedone and bis(6-aminopyrimidin-4-one) in acetic acid led to the formation of the corresponding bis(pyrimido[4,5-b]quinoline-4,6-diones) which are known as bis(sulfanediyl)bis(tetrahydro-5-deazaflavin) analogs in a single step. Also, bis(pyrimido[4,5-b]quinoline-4,6-diones) which are linked to naphthyl core via phenoxymethyl linkage is prepared. The interactions of the synthesized compounds with DNA and bovine serum albumin (BSA) were studied. Gel electrophoresis assay was used to show the capability of the compounds to photocleave the supercoiled pBR322 plasmid DNA in UV-A (365 nm). Besides, the most photocleavable compound, bis(tetrahydropyrimido[4,5-b]quinoline-4,6-dione) linked to pyridin-3-yl at position-5 exhibits good binding affinities toward CT-DNA and BSA as supported by UV/VIS spectral studies. In addition to the experimental findings, a molecular docking simulation was performed to collect detailed binding data for this compound to both biomolecules.

Pattern of novel psychoactive substance use among patients presented to the poison control centre of Ain Shams University Hospitals, Egypt: A cross-sectional study.

Background: Novel psychoactive substances (NPSs) are relatively new substances in the illicit drug market, not previously listed in the United Nations Office on Drugs and Crime (UNDOC). Strox and Voodoo are considered some of the most popular blends of NPS in the Egyptian drug market. Objectives: The current study was conducted to assess NPS's use pattern: Voodoo and Strox among acutely intoxicated patients presented to the poison control center of Ain Shams University Hospitals (PCC- ASUH). Methods: A single center based cross-sectional study was carried out in the PCC-ASUH among acutely intoxicated patients presenting to the emergency department (ED) over four months (from January-April 2019. using a previously adopted and validated Fahmy and El-Sherbini socioeconomic scale (SES). Data were presented as mean, median and range as appropriate. Both smoking and crowding indexes were calculated and presented as previously reported. Results: Fifty-one patients were presented to the ED of PCC-ASUH during the study period. A total of 96.1% (n = 49) were males. The mean age was 25 ± 7.5 years. The most common NPS used was Strox: 54.9% (n = 28), followed by Voodoo: 27.4% (n = 14). Neurological and gastrointestinal (GI) symptoms were the most frequent presentations. The most common motive behind NPS use was the desire to give a trial of new psychoactive substances. The mean SES score was 35.1 ± 13.17. Most patients have the preparatory as the highest education 36.0% (n = 18). Conclusions: NPS use is common among young males in preparatory education from different social classes, starting it most commonly as a means to experiencing a new high. Neurological and GI manifestations are the most common presenting symptoms of NPS intoxication.

Molecular characterization of a Novel NAD+-dependent farnesol dehydrogenase SoFLDH gene involved in sesquiterpenoid synthases from Salvia officinalis.

Salvia officinalis is one of the most important medicinal and aromatic plants in terms of nutritional and medicinal value because it contains a variety of vital active ingredients. Terpenoid compounds, particularly monoterpenes (C10) and sesquiterpenes, are the most important and abundant among these active substances (C15). Terpenes play a variety of roles and have beneficial biological properties in plants. With these considerations, the current study sought to clone theNAD+-dependent farnesol dehydrogenase (SoFLDH, EC: 1.1.1.354) gene from S. officinalis. Functional analysis revealed that, SoFLDH has an open reading frame of 2,580 base pairs that encodes 860 amino acids.SoFLDH has two conserved domains and four types of highly conserved motifs: YxxxK, RXR, RR (X8) W, TGxxGhaG. However, SoFLDH was cloned from Salvia officinalis leaves and functionally overexpressed in Arabidopsis thaliana to investigate its role in sesquiterpenoid synthases. In comparison to the transgenic plants, the wild-type plants showed a slight delay in growth and flowering formation. To this end, a gas chromatography-mass spectrometry analysis revealed that SoFLDH transgenic plants were responsible for numerous forms of terpene synthesis, particularly sesquiterpene. These results provide a base for further investigation on SoFLDH gene role and elucidating the regulatory mechanisms for sesquiterpene synthesis in S. offcinalis. And our study paves the way for the future metabolic engineering of the biosynthesis of useful terpene compounds in S. offcinalis.

Spectroscopic Behavior and Photophysical Parameters of 2-(Acetoxymethyl)-6-(1,2,4-triazinylaminodihydroquinazolinyl)tetrahydropyran Derivative in Different Solid Hosts.

Optical and photophysical properties of 6-substituted-1,2,4-Triazine fluorescent derivative dye doped in silicate based sol-gel, homopolymer of methyl methacrylate (PMMA), and copolymer (MMA/diethylene glycol dimethacrylate) (DEGDMA) were investigated. The pores of different hosts and caging of the dye were found to effect on the parameters such as molar absorptivity, cross sections of singlet-singlet electronic absorption and emission spectra, excited state lifetime, quantum yield of fluorescence. The dipole moment of electronic transition, the length of attenuation and oscillator strength of electronic transition from So → S1 have been calculated. The dye was pumped with different powers using 3rd harmonic Nd: YAG laser of 355 nm and pulse duration 8 ns, with repetition rate 10 Hz. Good photo stability for dye was attained. After 55,000 pumping pulses of (10 mJ/pulse), the photo-stabilities were decreased to 53%, 48%, and 45% of the initial ASE of dye in sol gel, PMMA, and Co-polymer respectively. The dye in sol-gel matrix showed improvement of photo stability compared with those in organic polymeric matrices.

Chitosan Schiff bases-based polyelectrolyte complexes with graphene quantum dots and their prospective biomedical applications.

Chitosan (Cs) bis-aldehyde Schiff base derivatives were synthesized by condensation of Cs with three bis-aldehydes namely; butane-1,4-diyl bis(4-formylbenzoate), N,N'-(butane-1,4-diyl)bis(2-(4-formylphenoxy)acetamide) and 4,4'-(butane-1,4-diylbis(oxy))dibenzaldehyde. The prepared Cs derivatives were blended with carboxymethyl chitosan(CMC) and graphene quantum dots (GQDs) to produce semi-IPNs polyelectrolyte complexes (PECs). and characterized with respect to their molecular structure and physio-chemical properties. The antibacterial activity against H. pylori (and in vitro Inosine 5'-monophosphate dehydrogenase IMPDH inhibitory assay) was evaluated. Additionally, a preliminary in vitro assessment for wound healing was performed against PECs in which wound closure percentages, and rates were investigated indicating an accelerated wound healing compared with untreated cells. The PEC based on Schiff base PEC containing amide linkage showed the highest wound healing ability. A minimal inhibitory concentration (MIC) was obtained for the PEC sample containing Cs Schiff base derived from 4,4'-(butane-1, 4-diylbis(oxy))dibenzaldehyde at a dose of 0.98 µg/ml inhibiting H. pylori growth by 100%. Additionally, the selected above-mentioned compound was selected to test its inhibitory activity against the HpIMPDH enzyme in addition to its selectivity towards the hIMPDH2 enzyme and was found to have promising activity against the HpIMPDH enzyme with IC50 value of 0.65 µM, and to be safer and less active against the hIMPDH2 enzyme with IC50 > 10 µM, reflecting its selectivity.

Spectral Behavior and Photophysical Parameters of Dihydrophenanthro[9,10-e][1,2,4]Triazine Derivative Dyes in Sol-Gel and Methyl Methacrylate Polymer Matrices.

This paper deals with the optical and photophysical properties of dihydrophenanthro[9,10-e][1,2,4]triazine fluorescent dyes doped in Silicate based sol-gel and homo-poly methyl methacrylate (PMMA). Solid hosts were found to effect on the optical and photophysical parameters such as molar absorptivity, cross sections of singlet-singlet electronic absorption and emission spectra, excited state lifetime, quantum yield of fluorescence. The dipole moment of electronic transition, the length of attenuation and oscillator strength of electronic transition from So → S1 have been calculated. The dyes were pumped with different powers using 3rd harmonic Nd:YAG laser of 355 nm and pulse duration 8 ns, with a repetition rate at (10 Hz). Good photostability for compounds 1 and 2 were attained. It was decreased to 49% & 54% and 46% & 40% of the initial ASE of dyes in sol gel and PMMA, respectively, after 55,000 pumping pulses at (10 mJ/pulse). The dyes in sol-gel showed improved photostability compared with those in organic polymeric matrices.

Application of a new system for classifying root and canal anatomy in studies involving micro-computed tomography and cone beam computed tomography: Explanation and elaboration.

Adequate knowledge and accurate characterization of root and canal anatomy is an essential prerequisite for successful root canal treatment and endodontic surgery. Over the years, an ever-increasing body of knowledge related to root and canal anatomy of the human dentition has accumulated. To correct deficiencies in existing systems, a new coding system for classifying root and canal morphology, accessory canals and anomalies has been introduced. In recent years, micro-computed tomography (micro-CT) and cone beam computed tomography (CBCT) have been used extensively to study the details of root and canal anatomy in extracted teeth and within clinical settings. This review aims to discuss the application of the new coding system in studies using micro-CT and CBCT, provide a detailed guide for appropriate characterization of root and canal anatomy and to discuss several controversial issues that may appear as potential limitations for proper characterization of roots and canals.

Mycobiota associated with strawberry fruits, their mycotoxin potential and pectinase activity.

Forty-three species and variety belonging to 15 genera were collected from 30 strawberry fruit samples on Glucose-Czapek's agar medium. Among them, Aspergillus flavus, Aspergillus niger and Penicillium citrinum were the most frequent species recovered from 53.3%, 70.0% and 50.0% of the samples, respectively. According to the ITS rDNA sequence, we confirmed the morphological identification result. Moreover, aflatoxin biosynthesis gene omt-A was detected in A. flavus, while Aopks gene was found in A. niger. Interestingly, we could not detect any aflatoxin or ochratoxin biosynthesis genes in the P. citrinum strain. The concentration of detected aflatoxin was 3.5 ppb produced by A. flavus, while A. niger gave 4.1 ppb as ochratoxin. A. flavus was the most pectinase producer among the selected strains, and the highest amount was obtained at 30°C after 6 days of incubation with initial medium pH 8.