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.

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.

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.

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.

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.

Application of a new system for classifying tooth, root and canal morphology in the primary dentition.

Knowledge of root and canal morphology is essential for the effective practice of root canal treatment. Paediatric endodontics aims to preserve fully functional primary teeth in the dental arch; however, pulpectomy procedures in bizarre and tortuous canals encased in roots programmed for physiologic resorption are unique challenges. A new coding system for classifying the roots and main canals (https://doi.org/10.1111/iej.12685), accessory canals (https://doi.org/10.1111/iej.12800) and developmental anomalies (https://doi.org/10.1111/iej.12867) has been introduced recently. This paper discusses challenges for describing root and canal morphology in primary teeth and describes the potential application of the new classification system for root canals in the primary dentition.

Application of a new system for classifying root canal morphology in undergraduate teaching and clinical practice: a national survey in Malaysia.

AIM: To evaluate and compare the feedback of final year undergraduate dental students in eight Malaysian dental schools on the application of a new system for classifying root canal morphology in teaching and clinical practice. METHODS: One PowerPoint presentation describing two classification systems for root canal morphology (Oral Surgery Oral Medicine Oral Pathology, 1974 38, 456 and its supplemental configurations, International Endodontic Journal 2017, 50, 761) was delivered to final year undergraduate dental students in eight dental schools in Malaysia by two presenters (each presented to four schools). To examine students' feedback on the utility of each system, printed questionnaires consisting of six questions (five multiple choice questions and one open-ended question) were distributed and collected after the lecture. The questionnaire was designed to compare the classification systems in terms of accuracy, practicability, understanding of root canal morphology and recommendation for use in pre-clinical and clinical courses. The exact test was used for statistical analysis, with the level of significance set at 0.05 (P = 0.05). RESULTS: A total of 382 (out of 447) students participated giving a response rate of 86%. More than 90% of students reported that the new system was more accurate and more practical compared with the Vertucci system (P < 0.001). Overall, 97% of students reported the new system helped their understanding of root and canal morphology compared with the Vertucci classification (P < 0.001). Over 97% of students recommended the use of the new system in teaching, pre-clinical courses and clinical practice (P < 0.001). Except for two schools, no significant difference was detected between the responses of students for all questions at the different schools (P > 0.05). The students' responses for all questions were almost similar for both presenters (P > 0.05). CONCLUSIONS: The new system of International Endodontic Journal 2017, 50, 761 for classifying root and canal morphology was favoured by final year undergraduate dental students in Malaysia. The new system has the potential to be included in the undergraduate endodontic curriculum for teaching courses related to root and canal morphology.

Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents.

Ethyl 2-acrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as well as its corresponding bis-derivatives, 5-10, with aliphatic linkers were synthesized, fully characterized, and tested as novel anticancer agents. The targeted compounds, 5-10, were obtained by the Knoevenagel condensation reactions of bis-o- or -p-aldehyde with a molar ratio of ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate of 2 in the presence of piperidine in excellent yields (93-98%). The in vitro anticancer activities of the prepared compounds were evaluated against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC50 values of 13.5 and 32.2 µg/ml, respectively, against HepG2 cells, compared with the reference drug doxorubicin (IC50 : 21.6 µg/ml). Real-time reverse-transcription polymerase chain reaction was used to measure the changes in expression levels of the COL10A1 and COL11A1, ESR1, and ERBB2, or AXIN1 and CDKN2A genes within the treated cells, as genetic markers for colon, breast, or liver cancers, respectively. Treatment of the colon cancer cells with compounds 5, 9, and 10, or breast and liver cancers cells with compounds 7, 8, 9, and 10 downregulated the expression of the investigated tumor markers. The DNA damage values (depending on comet and DNA fragmentation assays) increased significantly upon treatment of colon cancer cells with compounds 5, 9, and 10, and breast and liver cells with compounds 8, 9, and 10. The structure-activity relationship suggested that the increase of the chain of the alkyl linker increases the anticancer activity and the compounds with bis-cyanoacrylamide moieties are more active than those with one cyanoacrylamide moiety.

Rapid detection of biomolecules in a dielectric modulated GaN MOSHEMT.

Biosensors are the devices that find application in almost every field nowadays. In this paper, GaN MOSHEMT based biosensor is proposed for detection of biomolecules such as ChOx, protein, streptavidin and Uricase. The effect of biomolecule species on the performance parameters of the device has been studied. It has been observed that there is a significant increase in the drain current and gd is observed with the addition of biomolecule in the nanocavity. The electron concentration contour is studied which shows the rise of carrier concentration with biomolecule. Maximum positive shift is observed in threshold voltage for Uricase due to lowest dielectric constant. Similarly, the change in transconductance is also obtained with biomolecules. The effect of cavity dimensions on sensitivity is also studied. The maximum increase of 10% in channel potential is noted due biomolecule presence in the cavity. This device has shown good sensing and can be used for biosensing applications efficiently in addition to the high power performance of MOS-HEMTs.

Root and canal morphology of maxillary premolar teeth in an Egyptian subpopulation using two classification systems: a cone beam computed tomography study.

AIM: To investigate the number of roots and root canal configurations using two coding systems and the root canal diverging and merging levels in extracted maxillary premolars in an Egyptian subpopulation using cone beam computed tomography (CBCT). METHODOLOGY: A total of 700 maxillary premolars were examined using CBCT in an Egyptian subpopulation. The number of roots was identified, and root canal configurations were classified according to Vertucci's classification and a new system for classifying root and canal morphology. In addition, the position where roots bifurcated and the levels where canals merged or diverged were identified. Fisher's exact test and independent t-test were used for statistical analysis, and the level of significance was set at 0.05 (P = 0.05). RESULTS: More than half of maxillary first premolars were double-rooted, and the majority of maxillary second premolars were single-rooted (P < 0.001). Most of the double-rooted samples had bifurcations in the middle of the root. According to the Vertucci classification, canal configuration type IV was the most common in both first and second maxillary premolars. According to the new system, the code 2 FP B1 P1 was the most common for maxillary first premolars, whilst 2 SP B1 P1 , 1 SP2 and 1 SP2-1 codes were the most common for maxillary second premolars. The three-canalled morphology in double- and three-rooted maxillary premolars had considerable variations. Root canal merging and diverging levels were comparable in both tooth types. CONCLUSION: Maxillary premolars in this Egyptian subpopulation had a wide range of root and canal anatomical variations. Clinicians should be aware of where canals merge and diverge to facilitate the treatment of all canals. The new system for classifying canal morphology describes the root and canal configurations in a more accurate and practical manner compared to the Vertucci classification.

Spectroscopic Study of Solvent Polarity on the Optical and Photo-Physical Properties of Novel 9,10-bis(coumarinyl)anthracene.

Novel 7,7'-((anthracene-9,10-diylbis(methylene))bis(oxy))bis(4-methyl-2H-chromen-2-one) (BisCA) was prepared as fluorescent probe. The chemical structure of the novel BisCA was confirmed by spectroscopic data as well as elemental analyses. The solvatochromic characteristics of the new proble and its precursors were investigated in different solvents including, ethanol, DMF and toluene as protic polar, aprotic polar and non-polar solvents, respectively. Photo-physical parameters of probes, such as fluorescence quantum yields, fluorescence lifetime of excited state, radiative and non-radiative decay, were assessed in different media. The intermolecular H-bond effect on absorption and excitation spectra of the novel probe was reported in different solvents. Also, Onsager cavity radius and dipole moment of ground state and excited state of the probe were calculated as described by Bakhshiev and Reichardt methods.

A new system for classifying accessory canal morphology.

Thorough knowledge of anatomical complexities of the root canal system has a direct impact on the effectiveness of canal preparation and filling, and is an essential prerequisite for successful root canal treatment. A wide range of complex variations in root canal anatomy exists, including root canal configuration type, developmental anomalies and minor canal morphology such as accessory canals and apical deltas. Accessory canals and apical deltas have been associated with pulp disease, primary canal infection, canal reinfection and post-treatment disease. The current definitions of accessory canal anatomy are not standardized and potentially confusing. Given their role in endodontic disease and their impact on treatment outcomes, there is a need to have a simple classification of their anatomy to provide an accurate description of their position and path from the canal to the external surface of the root. The purpose of this article is to introduce a new system for classifying accessory canal morphology for use in research, clinical practice and training.

A new system for classifying tooth, root and canal anomalies.

Understanding the normal anatomical features as well as the more unusual developmental anomalies of teeth, roots and root canals is essential for successful root canal treatment. In addition to various types of root canal configuration and accessory canal morphology, a wide range of developmental tooth, root and canal anomalies exists, including C-shaped canals, dens invaginatus, taurodontism, root fusion, dilacerations and palato-gingival grooves. There is a direct association between developmental anomalies and pulp and periradicular diseases that usually require a multidisciplinary treatment approach to achieve a successful outcome. A number of classifications have categorized tooth, root and canal anomalies; however, several important details are often missed making the classifications less than ideal and potentially confusing. Recently, a new coding system for classifying root, root canal and accessory canal morphology has been introduced. The purpose of this article is to introduce a new system for classifying tooth, root and canal anomalies for use in research, clinical practice and training, which can serve as complementary codes to the recently described system for classifying root, as well as main and accessory canal morphology.

Effect of root canal irrigation protocols on the dislocation resistance of mineral trioxide aggregate-based materials: A systematic review of laboratory studies.

The aim of this systematic review was to address the question: Do different irrigating protocols have an impact on the dislocation resistance of mineral trioxide aggregate (MTA)-based materials? The review was performed using a well-defined search strategy in three databases (PubMed, Scopus, Web of Science) to include laboratory studies performed between January 1995 and May 2017, in accordance with PRISMA guidelines. Two reviewers analysed the papers, assessed the risk of bias and extracted data on teeth used, sample size, size of root canal preparation, type of MTA-based material, irrigants, canal filling method, storage method and duration, region of roots and the parameters of push-out testing (slice thickness, plunger dimensions and plunger loading direction), the main results and dislocation resistance values (in MPa). From 255 studies, 27 were included for full-text analysis. Eight papers that met the inclusion criteria were included in this review. There was a wide variation in dislocation resistance due to differences in irrigation sequence, time and concentration of irrigants, storage method and duration, and the parameters of push-out bond strength testing. A meta-analysis was not done but qualitative synthesis of the included studies was performed. No definitive conclusion could be drawn to evaluate the effect of irrigation protocols on dislocation resistance of MTA-based materials. Recommendations have been provided for standardized testing methods and reporting of future studies, so as to obtain clinically relevant information and to understand the effects of irrigating protocols on root canal sealers and their interactions with the dentine walls of root canals.

Molecular docking simulation and anticancer assessment on human breast carcinoma cell line using novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) and bis(1,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-b]pyridine-6-carbonitrile) derivatives.

An efficient route for the synthesis of novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile) derivatives is reported. The synthetic pathway involves one pot, synthesis of bis-aldehydes, malononitrile, and pyrazolone in the presence of pyridine. The anticancer activity of the synthesized products against MCF7, HEPG2, and A549 cell lines was assessed. Docking studies were performed and indicated the best binding mode compared to the standard ligand sorafenib.

A new system for classifying root and root canal morphology.

Knowledge of root and root canal morphology is a prerequisite for effective nonsurgical and surgical endodontic treatments. The external and internal morphological features of roots are variable and complex, and several classifications have been proposed to define the various types of canal configurations that occur commonly. More recently, improvements in nondestructive digital image systems, such as cone-beam and micro-computed tomography, as well as the use of magnification in clinical practice, have increased the number of reports on complex root canal anatomy. Importantly, using these newer techniques, it has become apparent that it is not possible to classify many root canal configurations using the existing systems. The purpose of this article is to introduce a new classification system that can be adapted to categorize root and root canal configurations in an accurate, simple and reliable manner that can be used in research, clinical practice and training.

Accessory roots and root canals in human anterior teeth: a review and clinical considerations.

Anterior teeth may have aberrant anatomical variations in the number of roots and root canals. A review of the literature was conducted using appropriate key words in major endodontic journals to identify the available reported cases as well as experimental and clinical investigations on accessory roots and root canals in anterior teeth. After retrieving the full text of related articles, cross-citations were identified, and the pooled data were then discussed. Results revealed a higher prevalence in accessory root/root canal variations in mandibular anterior teeth than in maxillary counterparts. However, maxillary incisor teeth revealed the highest tendency for accessory root/root canal aberrations caused by anomalies such as dens invaginatus and palato-gingival groove. Primary anterior teeth may also exhibit external and internal anatomical variations in the root, especially maxillary canines. Therefore, dental practitioners should thoroughly assess all teeth scheduled for root canal treatment to prevent the undesirable consequences caused by inadequate debridement of accessory configurations of the root canal system.

Assessment of women's perspectives and experiences of childbirth and postnatal care using Q-methodology.

To complement standard measures of maternity care outcomes, an assessment of women's satisfaction with care is needed. The aim of this study was to elicit the perspectives and experiences of Iraqi women about childbirth and postnatal care services. The study participants were a sample of 37 women of different educational and socioeconomic status who had given birth during the previous 6 months. Q-methodology was used for data collection and analysis. Three distinct viewpoints and experiences of childbirth and postnatal care services were identified: a general perception of poor childbirth and postnatal care with lack of appropriate interpersonal care and support; a high satisfaction and positive experience with childbirth and postnatal care services among the confident and well-supported women; and poor satisfaction with the childbirth and postnatal care services in terms of meeting traditional cultural practices. Needs assessment around providers' skills and attitudes and the wider sociocultural environment of childbirth and postnatal care is necessary in Iraq.