(1R,2S,5R)-5-Methyl-2-[2-(4-nitrophenyl)propan-2-yl]cyclohexyl 2-(4-methoxyphenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate: crystal structure and Hirshfeld analysis

In the title compound, C28H34N2O5, the adjacent ester and nitrobenzene substituents are connected via an intramolecular methylene-C—H. ...(nitrobenzene) interaction and the molecule approximates to a U-shape. The dihydropyrrole ring (r.m.s. deviation = 0.003 A ˚ ) is almost co-planar with the carboxylate residue [Cm—N—C1—Oc (m = methine, c = carboxyl) torsion angle = 1.8 (4).] but is orthogonal to the 4-methoxybenzene ring [dihedral angle = 84.34 (17).]. In the crystal, methylene-C—H. ...O(carbonyl) interactions lead to linear supramolecular chains along the b-axis direction, which pack without directional interactions between them. The analysis of the calculated Hirshfeld surface points to the importance of weak interatomic H. . .H, O. . .H/H. . .O and C. . .H/H. . .C contacts in the crystal

(4-Nitrophenyl)methyl 2,3-dihydro-1H-pyrrole-1-carboxylate: crystal structure and Hirshfeld analysis

In the title compound, C12H12N2O4, the dihydropyrrole ring is almost planar (r.m.s. deviation = 0.0049 A ˚ ) and is nearly coplanar with the adjacent C2O2 residue [dihedral angle = 4.56 (9˚)], which links to the 4-nitrobenzene substituent [dihedral angle = 4.58 (8˚)]. The molecule is concave, with the outer rings lying to the same side of the central C2O2 residue and being inclined to each other [dihedral angle = 8.30 (7˚)]. In the crystal, supramolecular layers parallel to (105) are sustained by nitrobenzene-C—H...O(carbonyl) and pyrrole-C—H...O(nitro) interactions. The layers are connected into a three- dimensional architecture by π(pyrrole)–π(nitrobenzene) stacking [inter-centroid separation = 3.7414 (10) A ˚ ] and nitro-O...π(pyrrole) interactions

1-Ethyl 2-methyl 3,4-bis(acetyloxy)pyrrolidine-1,2-dicarboxylate: crystal structure, Hirshfeld surface analysis and computational chemistry

The title compound, C13H19NO8, is based on a tetra-substituted pyrrolidine ring, which has a twisted conformation about the central C—C bond; the Cm—Ca—Ca—Cme torsion angle is 38.26 (15)° [m = methyl­carboxyl­ate, a = acet­yloxy and me = methyl­ene]. While the N-bound ethyl­carboxyl­ate group occupies an equatorial position, the remaining substituents occupy axial positions. In the crystal, supra­molecular double-layers are formed by weak methyl- and methyl­ene-C—H...O(carbon­yl) inter­actions involving all four carbonyl-O atoms. The two-dimensional arrays stack along the c axis without directional inter­actions between them. The Hirshfeld surface is dominated by H...H (55.7%) and H...C/C...H (37.0%) contacts; H...H contacts are noted in the inter-double-layer region. The inter­action energy calculations point to the importance of the dispersion energy term in the stabilization of the crystal

Ethyl 3,4-bis(acetyloxy)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate

The title pyrrolidine compound, C18H23NO7, is a tetra-substituted species in which the five-membered ring has a twisted conformation with the twist occurring in the C—C bond bearing the adjacent acet­yloxy substituents; the Cm—Ca—Ca—Cp torsion angle is −40.76 (18)° [m = methyl­ene, a = acet­yloxy and p = phen­yl]. The N atom, which is sp2-hybridized [sum of bond angles = 359.4°], bears an ethyl­carboxyl­ate substitutent and is connected to a methyl­ene-C atom on one side and a carbon atom bearing a 4-meth­oxy­phenyl group on the other side. Minor disorder is noted in the ethyl­carboxyl­ate substituent as well as in one of the acet­yloxy groups; the major components of the disorder have site occupancies of 0.729 (9) and 0.62 (3), respectively. The most notable feature of the mol­ecular packing is the formation of helical, supra­molecular chains aligned along the b-axis direction whereby the carbonyl-O atom not involved in a disordered residue accepts C—H...O inter­actions from methyl­ene-H and two-C atom separated methine-H atoms to form a six-membered {...HCCCH...O} synthon

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

X Ray Diffraction Structural Determination of Polyhydroxylated Pyrrolidines with iInhibitory Potential of Purine Nucleoside Phosphorylase

Foram determinadas por meio de difração de raios x as estruturas de cinco compostos azaçúcares. Foram estudadas as interações envolvidas na formação das redes cristalinas em cada um dos compostos analisados. Foi encontrado que nos compostos azaçúcares estudados, as interações principais são as ligações de hidrogênio do tipo C-H···O e C-H···π. Este comportamento foi verificado usando ferramentas como as superfícies de Hirshfeld e os gráficos de impressão digital. Realizou-se o estudo de docking molecular dos compostos azaçúcares com respeito à enzima purina nucleosídeo fosforilase (PNP). Foi determinado que estes compostos têm a capacidade de entrar no sitio ativo da PNP. O estudo das interações dos cinco azaçúcares com a PNP mostrou que estes compostos apresentam as mesmas interações presentes em inibidores da PNP já reportados.Structures of five azasugars were determined by X-ray diffraction. Crystal network interactions were analyzed for each compound. The main interaction found for these azasugar compounds is hydrogen bond as C-H···O e C-H···π. This behavior was verified by tools as Hirshfeld surface and 2D finger print plots. Molecular docking was performed for azasugar compounds in Purine Nucleoside phosphorylase (PNP). This study confirmed that these compounds are available to enter to the PNP active site. Interactions exploration showed the same interactions for the azasugars studied and for already known PNP inhibitors

Synthesis and characterization of mixed copper compounds with potential anti-Mycobacterium tuberculosis activity

No presente trabalho, foram estudadas duas series de complexos mistos de cobre (II). A primeira serie de complexos, constituída pelos ligantes 3-hidroxipicolinato e 2-acetilpiridinatiossemicarbazona N(4) substituída, sendo o substituinte variado pelos grupos ciclohexil, etil e fenil, ou o 2-acetilpiridinabenzilditiocarbazato. A segunda serie, constituída pelas mesmas tiossemicarbazonas e ditiocarbazato, com o ligante 2-hidroxinicotinato no lugar do 3-hidroxipicolinato. Com a finalidade de avaliar a atividade contra Mycobacterium tuberculosis. Os complexos obtidos foram caracterizados em estado sólido, pelo ponto de fusão e por meio espectroscopia de absorção na região do infravermelho e difração de raios X em monocristais. Em solução foi utilizada a técnica de espectroscopia eletrônica. Foi feito o estudo da atividade biológica dos 8 compostos obtidos contra o Mycobacterium tuberculosis, sendo todos eles candidatos ativos e promissores no combate à bactéria, já que apresentam todos valores baixos de concentração inibitória mínima. Sendo que os complexos 2 ,3, 4 e 6 apresentam atividade melhor do que alguns dos fármacos já usados no tratamento como ciprofloxacino, ácido p-aminosalicílico, cicloserina, gentamicina, etambutol, kanamicina, tobramicina, claritromicina e tiacetazona.In the present work were investigated two series of mixed complexes of coppe (II). The first of them is constituted by the ligands 3-hydroxypicolinate and 2-acetylpyridinedithiosemicabazate or 2-acetylpyridinethiossemicrzones N(4) substituted, were the substituted groups consist on cyclohexyl, ethyl and phenyl. The second series is formed by the same thiosemicarbazones and dithiocarbazate, but with the ligand 2-hydroxynicotinate, instead of 3-hydroxypicolinate. This, in order to evaluate the activity against Mycobaterium tuberculosis. The synthetized complexes have been characterized in solid state through the melting point and infrared spectroscopy and X-ray diffraction on single crystals. The characterization in solution was done by electronic spectroscopy. Assays were performed to determine the biological activity of the eight compounds synthetized against the Mycobacterium tuberculosis. All complexes have shown low minimal inhibitory concentration, being promising candidates for successive tests. It is observed that complex 2, 3, 4 and 6 exhibit better activity than some of the drugs used in the treatment such as ciprofloxacin, p-aminosalicylic acid, cycloserine, gentamicin, ethambutol, kanamycin, tobramycin, thiacetazone and clarithromycin

Developments in exploration and use of marine genetic resources

The ocean is home to a vast diversity of life forms constituting a rich source of marine genetic resources, that is, genetic material of marine origin containing functional units of heredity of actual or potential value, characterized by high biological and chemical diversity (Appeltans and others, 2012; United Nations, 2017). Over 34,000 marine natural products have been described, with recent discovery rates reaching more than 1,000 compounds each year (Lindequist, 2016; Carroll and others, 2019). A total of 188 new marine natural products from deep-sea organisms (Bryozoa, Chordata, Cnidaria, Echinodermata, Mollusca, Porifera and microbes) have been described since 2008 (Skropeta and Wei, 2014). Approximately 75 per cent of those novel products have remarkable bioactivity, with 50 per cent exhibiting moderate to high cytotoxicity towards a range of human cancer cell lines. Although the bioactivity of many marine natural products suggests high potential for drug discovery, only 13 marine-derived drugs have gained market approval to date (Liang and others, 2019; Mayer and others, 2010).5 However, at the time of writing, 28 candidates were in clinical trials (Alves and others, 2018). Marine antifoulant research is currently focused on identifying viable non-toxic substances, and a recent review has estimated that more than 198 antifouling compounds have been obtained from marine invertebrates, specifically sponges, gorgonians and soft corals (Qi and Ma, 2017), in addition to the products derived from macroalgae and microalgae highlighted in the first World Ocean Assessment (United Nations, 2017). Innovative research has also identified ingredients from discarded fish that are suitable for use in high-end cosmetics and a number of other products (Young, 2014). As of 2018, a total of 76 publicly available cosmeceutical ingredients from marine natural products had been marketed, reflecting a new growth sector (Calado and others, 2018). At the same time, consumer demand for nutraceuticals has increased rapidly, as foreseen in the first Assessment. The global nutraceutical market is expected to reach $580 billion by 2025, more than triple the$180 billion projected for 2017 in the first Assessment, and market growth has been linked to increased innovation and consumer awareness (Grand 6 See Midwestern University, “Clinical Pipeline, Marine Pharmacology”.View Research, 2017). Marine nutraceutical products such as fish oil and collagen represent a large portion of the global market, and demand for those products is expected to grow in the Asia-Pacific region, in particular in China and India (Suleria and others, 2015). While marine genetic resources are of growing importance to the global blue economy, most commercial activity is concentrated in a comparatively small number of countries, suggesting that there is potential for technology transfer and capacity-building (Thompson and others, 2017; Blasiak and others, 2018). Several international processes addressing genetic resources, including marine genetic resources, are currently under way.Fil: Blasiak, Robert. Stockholm Resilience Centre; SueciaFil: Kenchington, Ellen. Bedford Institute Of Oceanography; CanadáFil: Arrieta, Jesús M.. Instituto Español de Oceanografia; EspañaFil: Bermúdez Monsalve, Jorge Rafael. Escuela Superior Politécnica del Litoral; EcuadorFil: Calumpong, Hilconida. Silliman University; FilipinasFil: Changwei, Shao. Yellow Sea Fisheries Research Institute; ChinaFil: Chiba, Sanae. Marine Biodiversity And Environmental Assessment Resear; JapónFil: Dionisi, Hebe Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; ArgentinaFil: Garcia Soto, Carlos. Instituto Español de Oceanografia; EspañaFil: Vieira, Helena. Universidad de Lisboa; PortugalFil: Wawrik, Boris. United States Department Of Energy; Estados Unido

Additional file 7 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Additional file 7. Sensitivity analyses: various meta-analytic approaches

Additional file 2 of Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials

Additional file 2. Email invitation