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Objectives: Examining the cumulative evidence from randomized controlled trials (RCTs), evaluating the use of pharmacological agents for the treatment of COVID‐19 infections in patients with critical illness. Data Sources: Databases Medline, Embase, Web of Science, Scopus, CINAHL, and Cochrane. Study Selection: Inclusion criteria were RCTs that enrolled patients with confirmed or suspected COVID‐19 infection who are critically ill. Only RCTs that examined therapeutic agents against one another or no intervention, placebo, or standard of care, were included. Data Extraction: Pairs of reviewers extracted data independently. Outcomes of interest included the overall reported mortality defined as either the ICU mortality, hospital mortality, mortality within 28 days or mortality within 90 days. Data Synthesis: A total of 40 studies (11,613 patients) evaluated 50 therapeutic intervention arms divided into five main therapy categories; steroids, antiviral medications, immunomodulators, plasma therapies [intravenous immunoglobulins (IVIG), convalescent plasma and/or, therapeutic plasma exchange], and therapeutic anticoagulation. Immunomodulators was the only group with possible mortality benefit, risk ratio (RR) 0.83 (95% CI 0.73; 0.95), with nonsignificant heterogeneity (I2 = 8%, p = 0.36). In contrast, the other therapy groups showed no significant impact on mortality, as indicated by their respective pooled RRs: steroids [RR 0.91 (95% CI 0.82; 1.01), I2 = 31%], antiviral medications [RR 1.11 (95% CI 0.82; 1.49), I2 = 57%], plasma therapies [RR 0.77 (95% CI 0.58; 1.01), I2 = 36%], and anticoagulation [RR 1.06 (95% CI 0.95; 1.18), I2 = 0%]. Conclusions: This meta‐analysis highlights both the heterogeneity and a lack of benefit from therapies evaluated during the COVID‐19 pandemic. Many of the RCTs were developed based on limited observational data. Future RCTs investigating pharmaceutical interventions in critically ill patients during pandemics need to be designed based on better evidence. [ABSTRACT FROM AUTHOR]

A novel series of S‐alkylated, N‐alkylated, and N‐glycosylated 2‐thiohydantoin derivatives were synthesized via the reaction of (E)‐5‐(arylidene)‐1‐phenyl‐2‐thiohydantoins 5a–d with alkyl halides/glycosyl bromides under aqueous, anhydrous alkaline/glycosylation conditions, respectively. The structures of the novel compounds were confirmed by elemental analyses and spectral data. Computational studies using DFT calculations with B3LYP/6‐31 + G (d,p) level were performed to study the electronic and geometric properties obtained from the stable structure of the investigated compounds. A good correlation was found between the quantum chemical parameters and experimental observations. The synthesized derivatives exhibited good binding interactions towards the cyclin‐dependent kinase 2, especially (E)‐5‐(chlorobenzylidene)‐3‐(2′0.3′0.4′0.6′‐tetra‐O‐acetyl‐β‐d‐galactopyranosyl)‐1‐phenyl‐2‐thiohydantoin (11g), which have good key interactions such as the co‐crystallized ligand. In addition, it had selective cytotoxic activities with IC50 = 12.4 μM against lung cancer A549 cells. [ABSTRACT FROM AUTHOR]

A series of nanometer‐sized spherical sulfonamide imine ligands HL1‐HL5 and their copper and zinc complexes were synthesized and fully characterized based on elemental analyses, spectroscopic (UV/vis, FT‐IR, NMR, EPR, SEM) studies, molar conductance and thermal analyses. Furthermore, computational studies of HL1‐HL5 were carried out by the DFT/B3LYP method. TD‐DFT, HOMO and LUMO energy values, chemical hardness, electronegativity, electrophilic index, softness, and other parameters were calculated. Screening against several pathogenic microorganisms indicated that HL1 exhibited high activity against the tested Gram‐negative bacteria relative to other analogues and the inhibition activity is greater than the standard Gentamicin. Analogously, HL2 exhibited high potent activity against the tested Gram‐positive bacteria. Copper complexes exhibited a higher potent activity than zinc analogues. Noteworthy, inhibition activity of [Cu (L3)(OAc)] complex is higher than that of the standard Ampicillin. [Cu (L2)(OAc)] complex displayed a similar activity of the standard bactericides and fungicides in use. The complexes showed appreciated values of MIC against bacterial strains: B. subtilis (MIC = 0.4 μg / mL), E. coli and S. pneumonia (MIC = 1.95 μg / mL) and P. aeruginosa (MIC = 7.81 μg / mL). in vitro cytotoxic activities study proved that [Cu (L3)(OAc)] complex exhibited appreciable activity versus (HEPG‐2); IC50 = 4.8 μg/ml, while [Cu(L2)(OAc)] complex showed a high activity against (MCF‐7); IC50 = 6.2 μg/ml. These results could be considered as new findings of promising antitumor candidates for experimental chemotherapy. [ABSTRACT FROM AUTHOR]

The molecular structures of the so‐called azo dye and its Zn (II) and Cd (II) complexes were predicted in the present manuscript: 2,4‐dihydroxy‐5‐[(5‐mercapto‐1H‐1,2,4‐triazole‐3‐yl) diazenyl] benzaldehyde(H2L). The analyses elemental and thermal, spectra (FT‐IR, MS, UV–Vis), DFT/B3LYP/GENECP at which 6‐31G** basis set is used for C, H, N, O and S and LANL2DZ for Cd and Zncalculations and conductivity, the structures of these newly synthesized complexes were allocated. The small conductivity values exposed the non‐electrolytic nature. TGA curves used Coats‐Redfern to calculate the activation parameters for the thermal decomposition phases. The interaction between calf thymus DNA and investigated compounds was explored through UV–visible measurements of absorption and viscosity. The findings stated that through intercalative binding mode, the complexes communicate with DNA by calculating the constants of binding. In addition, the antimicrobial activity for the ligand and complexes in vitro were tested. The calculations demonstrate that the investigated complexes have octahedral geometry which agrees with the experimental observations. Molecular docking simulation was conducted using molecular operator environment (MOE) for ligand (H2L), Zn (II) and Cd (II) complexes. The docking calculations verified that the Zn (II)‐complex has greater potency and affinity to the (GLUT1) protein than those of the ligand and Cd (II)‐complex, which is inconsistent with the experimental activity. Finally, quantum mechanical and molecular docking are effective methods to better describe the studied molecules 'biological activity. [ABSTRACT FROM AUTHOR]

The absolute necessity to fight some class of tumor is perceived as serious health concerns, so the discovery and development of effective anticancer agents are urgently needed. (E)‐4‐((2‐hydroxyphenyl)diazenyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one, HL, and its Ni(II), Pd(II) and Pt(II) complexes were synthesized and the biological activity was evaluated for antitumor, antioxidant and antimicrobial activity as well as DNA cleavage. Their structures were assigned depending on the elemental analysis, conductivity, magnetic moment, spectral measurements (IR, 1HNMR, mass and UV–Vis) and thermal analysis. 3D molecular modeling using DFT method confirmed that the geometrical structures agree well with the suggested experimental ones. The antitumor activity was evaluated against four different cell lines using MTT assay. The ligand HL showed a potent cytotoxic activity compared to 5‐fluorouracil as a reference drug. For metal complexes, the order of activity was: Pd(II) > Ni(II) > Pt(II). A remarkable antioxidant activity for the ligand HL was recorded. It was higher than that of the metal complexes. Results of antimicrobial experiments revealed that all compounds were moderate to highly active against selected bacterial strains but inactive as antifungal except Pd(II) which showed a moderate antifungal activity. Gel electrophoresis showed insignificant nucleases activity for the ligand or its metal complexes even in the presence of H2O2 providing protection of DNA from damage. The antitumor activity of our compounds may be not due to DNA cleavage but may be referred to a mechanism similar to that of 5‐fluorouracil which interfere with DNA replication. The present work suggests the use of this ligand in the design and development of new anticancer drugs. [ABSTRACT FROM AUTHOR]

A series of organoiron complexes containing piperazine units have been synthesized via sequential nucleophilic aromatic substitutions. The structures and molecular properties of these complexes are investigated using various spectroscopic and analytical techniques. Cyclic voltammetric studies are conducted at various temperatures and the electrochemical analyses for the iron-containing macromolecules show broadening of the cathodic peak at a higher molecular weight linear chain. The molecular structures of the series of complexes are investigated using Merck molecular force field. All conformers show similar energies and a flexible structure. Scanning electron microscopy is also used to examine the surface morphology. Some of these complexes exhibit activity toward Gram-positive bacteria (Methicillin-resistant Staphylococcus aureus and Staphylococcus warneri), as well as MCF7 and HTB26 breast cancer cell lines. [ABSTRACT FROM AUTHOR]