Structure-activity relationships and molecular docking studies of chromene and chromene based azo chromophores

The design of novel materials with significant biological properties is a main target in drug design research. Chromene compounds represent an interesting medicinal scaffold in drug replacement systems. This report illustrates a successful synthesis and characterization of two novel series of chromene compounds using multi-component reactions. The synthesis of the first example of azo chromophores containing chromene moieties has also been established using the same methodology. The antimicrobial activity of the new molecules has been tested against seven human pathogens including two Gm+ve, two Gm-ve bacteria, and four fungi, and the results of the inhibition zones with minimum inhibitory concentrations were reported as compared to reference drugs. All the designed compounds showed significant potent antimicrobial activities, among of them, four potent compounds 4b, 4c, 13e, and 13i showed promising MIC from 0.007 to 3.9 μg/mL. In addition, antiproliferative analysis against three target cell lines was examined for the novel compounds. Compounds 4a, 4b, 4c, and 7c possessed significant antiproliferative activity against three cell lines with an IC50 of 0.3 to 2 μg/mL. Apoptotic analysis was performed for the most potent compounds via caspase enzyme activity assays as a potential mechanism for their antiproliferative effects. Finally, the computational 2D QSAR and docking simulations were accomplished for structure-activity relationship analyses

Effect of Biotitania and Titania Addition on Bioactivity and Antibacterial Properties of Calcium Silicate Cement

Introduction: Nanoparticles are gaining more interest in dentistry for their antimicrobial, physical as well as other properties. This study aimed to evaluate the effect of adding two types of nanoparticles (NPs) on calcium silicate hydraulic cement’s (CSHC) unique bioactivity and antibacterial properties. Methods and Materials: Biotitania/AgCl NPs were synthetized and characterized for its morphology, types of formed functional groups and crystalline AgCl using field emission scanning electron microscope (FE-SEM) equipped with energy-dispersive X-ray spectroscopy (EDS), X-ray diffractometer (XRD), Fourier transformation infrared spectroscopy (FT-IR) and thermo-gravimetric analysis (TGA). The former NPs and commercial titania (TiO2) NPs were added (0.5, 1.5 and 3-weight %) to commercial CSHS powder. A total of 140 disk-shaped specimens (10 mm×1 mm) were prepared (seven material groups per each test in addition to the eighth cell control group) to evaluate cell viability and alkaline phosphatase activity (ALP) after 3 and 12 days, respectively. All were incubated with mesenchymal stem cells. Antibacterial efficacy against Streptococcus mutans (S. mutans) was evaluated through the bacterial growth curve slopes while being in direct contact with the tested material groups for 18 h. Results: Addition of all NPs percentages had no significant effect (P>0.05) on cell viability in comparison to positive control CSHC. Commercial TiO2 NPs (0.5 weight %) had statistically significant lower values (P≤0.05) for bacterial growth curve slope. However, addition of all NPs percentages had significantly improved (P≤0.05) the ALP activity of CSHC with the most prominent effect to 3-weight% biotitania/AgCl NPs. Conclusion: Based on this in vitro study, addition of biotitania/AgCl NPs up to 3-weight% significantly improved the bioactivity of CSHC without having a significant negative impact on its antibacterial efficacy. Interestingly, the addition of commercial TiO2 even in small amounts can significantly improve CSHC antibacterial efficacy

Macrophage activation syndrome triggered by systemic lupus erythematosus flare: successful treatment with a combination of dexamethasone sodium phosphate, intravenous immunoglobulin, and cyclosporine:a case report

Abstract Background Macrophage activation syndrome is classified as a secondary form of hemophagocytic lymphohistiocytosis. It is a hyperinflammatory complication observed to be comorbid with a variety of autoimmune diseases, including adult-onset Still’s disease and systemic juvenile idiopathic arthritis. Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus, which, if untreated, can be fatal, though determining the optimum treatment strategy is still a challenge. Case presentation Herein, we report a case of macrophage activation syndrome in a 33-year-old Egyptian female as an unusual complication of a systemic lupus erythematosus flare in adult patients. Our patient was initially treated with a combination of intravenous methylprednisolone pulse therapy and intravenous immunoglobulin therapy, which was followed by a course of oral prednisolone and oral cyclosporine with little response. Switching from oral prednisone to intravenous dexamethasone sodium phosphate showed a more favorable clinical and biochemical response. Conclusion Macrophage activation syndrome is less commonly detected in adult patients with systemic lupus erythematosus. Our case demonstrates that dexamethasone sodium phosphate can be a successful alternative treatment for patients with systemic lupus erythematosus complicated by macrophage activation syndrome in whom the response to pulse methylprednisolone was inadequate to manage their illness, proving to be remarkably effective in a relatively short time frame

Clinical characteristics of depression among adolescent females: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Adolescents rarely seek psychiatric help; they even hesitate to disclose their feelings to their parents. However; the adolescents especially the females experience depressive symptoms more frequently than general population. Do they experience classic depressive symptoms? Are there symptoms specific to this subpopulation?</p> <p>Aim of the study</p> <p>Through this study, the authors aimed to estimate the prevalence of depressive disorders in Egyptian adolescent female students. They also expected a characteristic profile of symptoms for the adolescent females. However available literature provides no guidance in the description of this profile of symptoms.</p> <p>Methods</p> <p>A number of 602 adolescent females were interviewed, and subjected to General Health Questionnaire (GHQ); Children Depression Inventory (CDI), Structured Clinical Interview for DSM-IV Axis-I Disorders (SCID-I), then Hamilton Rating Scale for Depression (Ham-D). Results were analyzed by the use of SPSS-15.</p> <p>Results</p> <p>The study revealed the prevalence of depression in the sample of the study to be 15.3% (measured by CDI), and 13.3% (measured by SCID-I). Fatigue was the most common presenting depressive symptom (81.3%), in addition to other emotional, cognitive and physiological symptoms. Suicidal ideations were the most common suicidal symptoms in depressed adolescent females (20%), with 2.5% serious suicidal attempts.</p> <p>Conclusions</p> <p>The somatic symptoms were by far the most common presenting symptom for female adolescents suffering from depressive disorders. Depressive phenomena including unexplained fatigue, decreased energy, psychomotor changes, lack of concentration, weight changes and suicidal ideations may be the presenting complaints instead of the classic sad mood.</p

Modulation of limbic resting-state networks by subthalamic nucleus deep brain stimulation

Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson’s disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson’s disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF (p = 0.0057) and 49 age-matched healthy controls (p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared with healthy controls (p = 0.021), but not when STN-DBS was ON, which indicates rebalancing of this network. These results highlight the modulatory effect of STN-DBS on components of the limbic system, particularly within the orbitofrontal cortex, a structure associated with reward processing. These results reinforce the value of quantitative biomarkers of RSN activity in evaluating the disseminated impact of brain stimulation techniques and the personalization of therapeutic strategies

Modulation of limbic resting-state networks by subthalamic nucleus deep brain stimulation

Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson’s disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson’s disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF (p = 0.0057) and 49 age-matched healthy controls (p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared with healthy controls (p = 0.021), but not when STN-DBS was ON, which indicates rebalancing of this network. These results highlight the modulatory effect of STN-DBS on components of the limbic system, particularly within the orbitofrontal cortex, a structure associated with reward processing. These results reinforce the value of quantitative biomarkers of RSN activity in evaluating the disseminated impact of brain stimulation techniques and the personalization of therapeutic strategies

The Importance of Research on the Origin of SARS-CoV-2

The origin of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virus causing the COVID-19 pandemic has not yet been fully determined. Despite the consensus about the SARS-CoV-2 origin from bat CoV RaTG13, discrepancy to host tropism to other human Coronaviruses exist. SARS-CoV-2 also possesses some differences in its S protein receptor-binding domain, glycan-binding N-terminal domain and the surface of the sialic acid-binding domain. Despite similarities based on cryo-EM and biochemical studies, the SARS-CoV-2 shows higher stability and binding affinity to the ACE2 receptor. The SARS-CoV-2 does not appear to present a mutational “hot spot” as only the D614G mutation has been identified from clinical isolates. As laboratory manipulation is highly unlikely for the origin of SARS-CoV-2, the current possibilities comprise either natural selection in animal host before zoonotic transfer or natural selection in humans following zoonotic transfer. In the former case, despite SARS-CoV-2 and bat RaTG13 showing 96% identity some pangolin Coronaviruses exhibit very high similarity to particularly the receptor-binding domain of SARS-CoV-2. In the latter case, it can be hypothesized that the SARS-CoV-2 genome has adapted during human-to-human transmission and based on available data, the isolated SARS-CoV-2 genomes derive from a common origin. Before the origin of SARS-CoV-2 can be confirmed additional research is required

Comprehensive virtual screening of the antiviral potentialities of marine polycyclic guanidine alkaloids against SARS-CoV-2 (COVID-19)

The huge global expansion of the COVID-19 pandemic caused by the novel SARS-corona virus-2 is an extraordinary public health emergency. The unavailability of specific treatment against SARS-CoV-2 infection necessitates the focus of all scientists in this direction. The reported antiviral activities of guanidine alkaloids encouraged us to run a comprehensive in silico binding affinity of fifteen guanidine alkaloids against five different proteins of SARS-CoV-2, which we investigated. The investigated proteins are COVID-19 main protease (Mpro) (PDB ID: 6lu7), spike glycoprotein (PDB ID: 6VYB), nucleocapsid phosphoprotein (PDB ID: 6VYO), membrane glycoprotein (PDB ID: 6M17), and a non-structural protein (nsp10) (PDB ID: 6W4H). The binding energies for all tested compounds indicated promising binding affinities. A noticeable superiority for the pentacyclic alkaloids particularly, crambescidin 786 (5) and crambescidin 826 (13) has been observed. Compound 5 exhibited very good binding affinities against Mpro (∆G = −8.05 kcal/mol), nucleocapsid phosphoprotein (∆G = −6.49 kcal/mol), and nsp10 (∆G = −9.06 kcal/mol). Compound 13 showed promising binding affinities against Mpro (∆G = −7.99 kcal/mol), spike glycoproteins (∆G = −6.95 kcal/mol), and nucleocapsid phosphoprotein (∆G = −8.01 kcal/mol). Such promising activities might be attributed to the long ω-fatty acid chain, which may play a vital role in binding within the active sites. The correlation of c Log P with free binding energies has been calculated. Furthermore, the SAR of the active compounds has been clarified. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) studies were carried out in silico for the 15 compounds; most examined compounds showed optimal to good range levels of ADMET aqueous solubility, intestinal absorption and being unable to pass blood brain barrier (BBB), non-inhibitors of CYP2D6, non-hepatotoxic, and bind plasma protein with a percentage less than 90%. The toxicity of the tested compounds was screened in silico against five models (FDA rodent carcinogenicity, carcinogenic potency TD50, rat maximum tolerated dose, rat oral LD50, and rat chronic lowest observed adverse effect level (LOAEL)). All compounds showed expected low toxicity against the tested models. Molecular dynamic (MD) simulations were also carried out to confirm the stable binding interactions of the most promising most promising compounds, 5 and 13, with their targets. In conclusion, the examined 15 alkaloids specially 5 and13 showed promising docking,ADMET,toxicity and MD results which open the door for further investigations for them against SARS-CoV-2