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

Cognitive dysfunction among inpatients and outpatients with schizophrenia : relationship to positive and negative symptoms

Background: Cognitive impairment is an established feature of schizophrenia and is a strong predictor of eventual social and functional outcome. Few studies have investigated cognitive impairment in hospital long-stay patients with schizophrenia. This study evaluates and compares cognitive function among a sample of patients with schizophrenia in both inpatient and outpatient departments in order to determine the relationship between cognitive impairment and clinical variables. A cross-sectional comparative study based on a semi-structured interview investigating 100 inpatients with schizophrenia recruited from El-Abassia Mental Health Hospital departments compared to 100 patients with schizophrenia selected from the outpatients’ clinic matched with cases. The assessment tools included SCID-I, the Adult Wechsler Intelligence Scale, the computerized version of Wisconsin Card Sorting Test (WCST), Mini-Mental State Examination (MMSE), and Positive and Negative Syndrome Scale (PANSS). Results: Patients with schizophrenia showed significant deficits on cognitive function with no statistically significant difference between the inpatient and outpatient groups. Executive function was significantly correlated with verbal, non-verbal, and total IQ. Executive function was negatively correlated with the positive and general symptoms of PANSS and not correlated with its negative symptoms. In addition, we did not find any statistically significant relationship between cognitive functions and the duration of illness. Conclusion: The study provides evidence that institutionalization is not an influential factor on cognitive impairment patients with schizophrenia. However, the psychopathological aspects of the disorder are one of the crucial factors affecting the cognitive function in schizophrenia

Comorbidity of depression and type 2 diabetes in Egypt results from the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) study

Background: Diabetes mellitus and depression are serious common diseases, and the number of people with both conditions is rising steadily. Depression in people with diabetes mellitus results in poorer prognosis through different mechanisms. On the other hand, the presence of diabetes in individuals with depression increases functional impairment that is associated with depression. Aims: The study aimed to assess the prevalence and factors associated with depression among adults with type 2 diabetes mellitus attending a diabetes clinic in Cairo, Egypt. Methods: A cross-sectional study was conducted among adult patients with diabetes type 2 attending a diabetes clinic in the endocrinology department in Ain Shams University Teaching Hospital, Cairo, Egypt. Data were collected through face-to-face interviews by trained psychiatrists and from patients’ records. Results: The prevalence of depression among diabetic patients was 21.8% (95% CI [15.6%, 29.1%]). Depression was more common among younger age groups and those with a higher level of education. There was no significant difference between those with lifetime depression compared to those without depression regarding physical health complications. Conclusions: The prevalence of depression among patients with type 2 diabetes is high. Given the impact of co-morbid diabetes and depression, diabetic patients should be routinely screened for the latter condition

Management of bipolar disorder in the intercontinental region: an international, multicenter, non-interventional, cross-sectional study in real-life conditions

Most of the existing data on real-life management of bipolar disorder are from studies conducted in western countries (mostly United States and Europe). This multinational, observational cohort study aimed to describe the management and clinical outcomes of bipolar patients in real-life conditions across various intercontinental countries (Bangladesh, Egypt, Iran, Israel, Tunisia, and Ukraine). Data on socio-demographic and disease characteristics, current symptomatology, and pharmacological treatment were collected. Comparisons between groups were performed using standard statistical tests. Overall, 1180 patients were included. The median time from initial diagnosis was 80 months. Major depressive disorder was the most common initial diagnosis. Mood stabilizers and antipsychotics were the most common drugs being prescribed at the time of the study. Antidepressants (mainly selective serotonin uptake inhibitors [SSRIs]) were administered to 36.1% of patients. Patients with bipolar I disorder received higher number of antipsychotics and anxiolytics than those with bipolar II disorder (p < 0.001). Presence of depressive symptoms was associated with an increase in antidepressant use (p < 0.001). Bipolar disorder real-life management practice, irrespective of region, shows a delay in diagnosis and an overuse of antidepressants. Clinical decision-making appears to be based on a multidimensional approach related to current symptomatology and type of bipolar disorder

Results of the COVID-19 mental health international for the general population (COMET-G) study.

INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study. MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively. STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables. RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed. CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them

Heart-type fatty acid-binding protein detects more patients with non-ST segment elevation myocardial infarction compared to troponin-T

Objective: To assess the value of using heart-type fatty acid-binding protein (H-FABP) as a marker of acute myocardial infarction (AMI) in patients presenting with non-ST segment elevation ACS (NSTE-ACS) in comparison with troponin-T (cTnT). Methods: 122 consecutive patients presented with ischemic-type chest pain within the first 4 h of symptom onset with NSTE-ACS. Blood samples were obtained on arrival for H-FABP and cTnT. Patients with cTnT negative test on admission had a repeat analysis 6 h later. Patients with both H-FABP negative and admission cTnT positive had repeat analysis of H-FABP 6 h later. Results: On admission, H-FABP was positive in 84 patients (68.9%) versus 36 patients (29.5%) with cTnT (p = 0.032). On repeat analysis after 6 h, total number of cTnT positive patients was 94 (77%) and cTnT negative was 28 (23%). All cTnT negative patients had negative H-FABP. Of cTnT positive patients, 84 (89.4%) had positive H-FABP test while the remaining 10 (10.6%) had “false” negative results. Using the final results of cTnT positive as gold standard, early assessment of cTnT within 4 h of chest pain had sensitivity of 38.3% and specificity of 100% while H-FABP had sensitivity of 89.4% and specificity of 100%. Conclusions: For patients presenting with suspected ACS within 4 h of onset of symptoms, H-FABP detects a significantly larger number of patients with NSTEMI compared to troponin-T

Design of New Benzo[h]chromene Derivatives: Antitumor Activities and Structure-Activity Relationships of the 2,3-Positions and Fused Rings at the 2,3-Positions

A series of novel 4H-benzo[h]chromenes 4, 6–11, 13, 14; 7H-benzo[h]chromeno[2,3-d]pyrimidines 15–18, 20, and 14H-benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives 19a–e, 24 was prepared. The structures of the synthesized compounds were characterized on the basis of their spectral data. Some of the target compounds were examined for their antiproliferative activity against three cell lines; breast carcinoma (MCF-7), human colon carcinoma (HCT-116) and hepatocellular carcinoma (HepG-2). The cytotoxic behavior has been tested using MTT assay and the inhibitory activity was referenced to three standard anticancer drugs: vinblastine, colchicine and doxorubicin. The bioassays demonstrated that some of the new compounds exerted remarkable inhibitory effects as compared to the standard drugs on the growth of the three tested human tumor cell lines. The structure–activity relationships (SAR) study highlights that the antitumor activity of the target compounds was significantly affected by the lipophilicity of the substituent at 2- or 3- and fused rings at the 2,3-positions

Structural Characterization and Antimicrobial Activities of 7H-Benzo[h]chromeno[2,3-d]pyrimidine and 14H-Benzo[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c] pyrimidine Derivatives

Three new series of chromene molecules have been synthesized in order to explore their antimicrobial activity. The series encompass 2-substituted 14-(4-halophenyl)-12-methoxy-14H-benzo[h]chromeno[3,2-e][1,2,4]-triazolo[1,5-c]pyrimidines 7a–o, 9-benzylideneamino-7-(4-halo-phenyl)-5-methoxy-8-imino-7H-benzo-[h]chromeno[2,3-d]pyrimidines 8a–b and 3-ethoxycarbonyl-14-(4-halophenyl)-12-methoxy-14H-benzo-[h]chromeno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-one derivatives 12a–b. The structure of these novel compounds were confirmed using IR, 1H- and 13C-NMR as well as MS spectroscopy. The new compounds were evaluated in vitro for their antimicrobial activity and it was demonstrated that 7H-benzochromenopyrimidine and derivatives of 14H-benzochromenotriazolopyrimidine exhibited the most promising antibacterial activities compared to the reference antimicrobial agents. The structure activity relationship (SAR) studies of the target compounds agreed with the in vitro essays and confirmed higher potent antimicrobial activity against some of the tested microorganisms

Introducing novel potent anticancer agents of 1H-benzo[f]chromene scaffolds, targeting c-Src kinase enzyme with MDA-MB-231 cell line anti-invasion effect

In our effort to develop novel and powerful agents with anti-proliferative activity, two new series of 1H-benzo[f]chromene derivatives, 4a–h and 6a–h, were synthesised using heterocyclocondensation methodologies under microwave irradiation condition. The structures of the target compounds were established on the basis of their spectral data, IR, 1H NMR, 13 C NMR, 13 C NMR-DEPT/APT, and MS data. The new compounds have been examined for their anti-proliferative activity against three cancer cell lines, MCF-7, HCT-116, and HepG-2. Vinblastine and Doxorubicin have been used as positive controls in the viability assay. The obtained results confirmed that most of the tested molecules revealed strong and selective cytotoxic activity against the three cancer cell lines. Moreover, these molecules exhibited weak cytotoxicity on the HFL-1 line, which suggested that they might be ideal anticancer candidates. The SAR study of the new benzochromene compounds verified that the substituents on the phenyl ring of 1H-benzo[f]chromene nucleus, accompanied with the presence of bromine atom or methoxy group at the 8-position, increases the ability of these molecules against the different cell lines. Due to their high anti-proliferative activity, compounds 4c and 6e were selected to be examined their proficiency to inhibit the invasiveness of the highly sensitive and invasive breast cancer cell line, MDA-MB-231. The anti-invasion behaviour of these molecules against the highly sensitive, non-oestrogen, and progesterone MDA-MB-231 cell line gave rise to their decreasing metastatic effect compared to the reference drug. Furthermore, this report explores the apoptotic mechanistic pathway of the cytotoxicity of the target compounds and reveals that most of these compounds enhance the Caspase 3/7 activity that could be considered as potential anticancer agents