ZnO Nanocomposites of <i>Juniperus procera</i> and <i>Dodonaea viscosa</i> Extracts as Antiproliferative and Antimicrobial Agents

Cancer and microbial infections constitute a major burden and leading cause of death globally. The development of therapeutic compounds from natural products is considered a cornerstone in drug discovery. Therefore, in the present study, the ethanolic extract and the fractions of Dodonaea viscosa and Juniperus procera were evaluated for anticancer and antimicrobial activities. It was found that two fractions, JM and DC, exhibited promising anticancer and antimicrobial activities. The JM and DC fractions were further modified into ZnO nanocomposites, which were characterized by SEM, XRD, TGA, and EDX. It was noted that the synthesized nanocomposites displayed remarkable enhancement in cytotoxicity as well as antibacterial activity. Nanocomposite DC–ZnO NRs exhibited cytotoxicity with IC50 values of 16.4 ± 4 (HepG2) and 29.07 ± 2.7 μg/mL (HCT-116) and JM–ZnO NRs with IC50 values of 12.2 ± 10.27 (HepG2) and 24.1 ± 3.0 μg/mL (HCT-116). In addition, nanocomposites of DC (i.e., DC–ZnO NRs) and JM (i.e., JM–ZnO NRs) displayed excellent antimicrobial activity against Staphylococcus aureus with MICs of 2.5 and 1.25 μg/mL, respectively. Moreover, these fractions and nanocomposites were tested for cytotoxicity against normal fibroblasts and were found to be non-toxic. GC-MS analysis of the active fractions were also carried out to discover the possible phytochemicals that are responsible for these activities

Selective optical sensing of iron(III) ions in an aqueous medium by benzochromone-based Schiff Base and its application on test strips

In this work, we designed and synthesized a novel, simple, low-cost, and effective chromone–based Schiff base ligand (HL) and its application as a chemosensor for Fe3+ detection. The structure of the synthesized sensor bears carboxylic, azomethine, and carbonyl groups which act as chelating sites for the detection of Fe3+ ions. The chemosensor HL exhibited highly selective detection of Fe3+ via a significant color change from yellow to brown. The color change is due to the ligand-to-metal charge-transfer (LMCT) mechanism. The sensor (HL) was characterized using UV-Vis, FTIR, NMR (1H- and 13C), and mass spectroscopy. The ligand solubility, detection condition, and sensitivity assessment suggested optimal use of DMF-water (9:1 v/v) as a working solvent at pH 7.0. Among a list of 15 metal ions screened, HL was highly selective, with instant response, towards Fe3+ ions without significant interferences with the other metal ions. The complexation ratio and association constants of HL to Fe3+ was determined by Job’s plot and Benesi–Hildebrand methods, and were 2:1 and 2.24 × 103 M−1, respectively, with a detection limit of 2.86 μM. The HL probe was also applied to detect Fe3+ in real samples with acceptable performance. The simple test strips have been successfully developed and applied to the visual monitoring of Fe3 + ions with a detection limit of 68 µM. The DFT was used to examine the best interaction mode of HL with Fe metal to be Fe(III)–L or Fe(III)–2L. The chemical-reactivity and molecular electrostatic optional were figured to predict the interaction behavior of the tested compounds.</p

Synthesis and Biological Evaluation of 1,2,3-Triazole Tethered Thymol-1,3,4-Oxadiazole Derivatives as Anticancer and Antimicrobial Agents

A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these active derivatives, compound 2-(4-((5-((2-isopropyl-5-methylphenoxy)methyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol (9) was the best compound against all three tested cell lines, MCF-7 (IC50 1.1 μM), HCT-116 (IC50 2.6 μM), and HepG2 (IC50 1.4 μM). Compound 9 was found to be better than the standard drugs, doxorubicin and 5-fluorouracil. These compounds showed anticancer activity through thymidylate synthase inhibition as they displayed significant TS inhibitory activity with IC50 in the range 1.95–4.24 μM, whereas the standard drug, Pemetrexed, showed IC50 7.26 μM. The antimicrobial results showed that some of the compounds (6, 7, 9, 16, and 17) exhibited good inhibition on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The molecular docking and simulation studies supported the anticancer and antimicrobial data. It can be concluded that the synthesized 1,2,3-triazole tethered thymol-1,3,4-oxadiazole conjugates have both antiproliferative and antimicrobial potential

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Background: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60&nbsp;years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death.&nbsp;The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death

The value of open-source clinical science in pandemic response: lessons from ISARIC

International audienc

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use