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COVID-19 has affected more than half a billion people worldwide, with more than 6.3 million deaths, but the pathophysiological mechanisms involved in lethal cases and the host determinants that determine the different clinical outcomes are still unclear. In this study, we assessed lung autopsies of 47 COVID-19 patients and examined the inflammatory profiles, viral loads, and inflammasome activation. Additionally, we correlated these factors with the patient’s clinical and histopathological conditions. Robust inflammasome activation, mediated by macrophages and endothelial cells, was detected in the lungs of lethal cases of SARS-CoV-2. An analysis of gene expression allowed for the classification of COVID-19 patients into two different clusters. Cluster 1 died with higher viral loads and exhibited a reduced inflammatory profile than Cluster 2. Illness time, mechanical ventilation time, pulmonary fibrosis, respiratory functions, histopathological status, thrombosis, viral loads and inflammasome activation significantly differed between the two clusters. Our data demonstrated two distinct profiles in lethal cases of COVID-19, thus indicating that the balance of viral replication and inflammasome-mediated pulmonary inflammation led to different clinical outcomes. We provide important information to understand clinical variations in severe COVID-19, a process that is critical for decisions between immune-mediated or antiviral-mediated therapies for the treatment of critical cases of COVID-19.

Since the development of the Ullmann coupling in the early 20th Century, there has been intense and continuous research on the syntheses of biaryl compounds, which appears as an interesting branch of organic chemistry. A myriad of methodologies for the synthesis of biaryl compounds have been studied and well established, including homocoupling methodologies, which in general are robust as well as consolidated strategies. Biaryl systems are quite relevant building blocks for the synthesis of more complex chemical structures. Besides the diversity of functional groups that can be used to promote a new aryl-aryl bond, there is a wide variety of transition metals that can act as catalyst in these processes. In this review, we summarized numerous methodologies of homocoupling reactions for the synthesis of symmetrical biaryl compounds.

The synthesis of amidoglucals and glucal esters in good to high yields using 2-iodo-3,4,6-tri-O-acetyl-D-glucal as a substrate, Mo(CO)6 as a carbon monoxide source and PdCl2 as a catalyst is reported. This procedure shows advantages when compared to other published methodologies, as it is carried out in one pot relying on short reaction times at mild temperatures, under ligand-free conditions and with only one equivalent of Mo(CO)6.

The catalytic activity of metal–organic framework Cu(INA)2 (INA = isonicotinate ion) and the complex [Cu(INA)2(H2O)4] were studied in the Copper-catalyzed Azide–Alkyne Cycloaddition (CuAAC) and Biginelli reaction under solvent-free reaction conditions. The robust, efficient and eco-friendly new method allowed the preparation of a variety of 1,2,3-triazole compounds in good to excellent yields and high selectivity for the 1,4-disubstituted triazole. Moreover, for the Biginelli reaction between aldehydes, ethyl acetoacetate and urea, the corresponding dihydropyrimidinones (DHPMs) were also obtained in satisfactory yields under mild reaction conditions for both catalysts. The comparative study between Cu(INA)2-MOF and [Cu(INA)2(H2O)4] complex demonstrated better results for the Cu-MOF, for both the yields and the regioselectivity of the products. Furthermore, no change in the heterogeneous catalyst structure was observed after the reaction, allowing them to be recovered and reused without any loss of activity.

Chemical modifications of quinoline moiety have been recognized as a useful strategy to development of new drugs. Here, the cytotoxicity of a set of twenty-four 4-substituted quinolines (named HTI) was screened for their antitumor and antileishmanial potential in vitro, and the underlying mechanisms investigated. HTI 21 and HTI 22 exhibited the highest cytotoxicity, being selected to the subsequent studies. Both derivatives induced caspase-dependent apoptosis associated to the dissipation of the mitochondrial transmembrane potential (ΔΨ) and ROS generation. HTI-induced cell death was calcium dependent, associated to thiol oxidation and cysteine proteases activation. In isolated mitochondria, HTI derivatives promoted mitochondrial permeabilization by different mechanisms. The inhibition of BCL-2 by venetoclax enhanced the HTI-induced cytotoxicity. Regarding the inhibition of cysteine proteases type B of Leishmania mexicana, HTI 15 exhibited the most potent inhibitory activity through a linear non-competitive mechanism. These data highlight the therapeutic potential of 4-substituted quinolines as antitumor and antileishmanial drugs.

O presente artigo descreve a sintese de compostos bis(indolil)metanos (BIMs), a partir da reacao de alquilacao de Friedel-Crafts entre indois e aldeidos, catalisada por oxido de ferro nanoparticulado (Fe3O4 nano). As reacoes foram realizadas na ausencia de solvente a temperatura ambiente, sendo o catalisador recuperado magneticamente ao final das mesmas. A metodologia sintetica desenvolvida se mostrou simples e eficiente, levando a obtencao de uma serie de compostos BIMs em bons rendimentos (40-99 %) e de acordo com alguns principios da Quimica Verde, tais como: economia atomica, sintese segura, diminuicao de solventes e auxiliares, eficiencia energetica, nao formacao de derivados, catalise e quimica segura para a prevencao de acidentes.

The catalytic activity of metal-organic framework Cu(INA)

A carbonylative Sonogashira coupling approach to the synthesis of glyco-alkynones is described. Eighteen examples were obtained in moderate do nearly quantitative yields under mild conditions employing Mo(CO)

A carbonylative Sonogashira coupling approach to the synthesis of glyco-alkynones is described. Eighteen examples were obtained in moderate do nearly quantitative yields under mild conditions employing Mo(CO)6 as a safe carbon monoxide source. Functionalization of the alkynyl moiety via cycloaddition with organic azides provided six examples of glyco-triazoles.

A regioselective ytterbium-catalyzed annulation reaction between ethylglyoxalate, anilines and silyl-alkynes bearing selenyl- and telluryl-moieties for the formation of poly-substituted quinolones is described. A series of examples formed under mild conditions are presented, including a scaled-up reaction and a study on catalyst recyclability.

Selenium propargylamines were synthesized via an A3-coupling approach using piperidine, p-methoxybenzaldehyde, and trimethylsilyl selenium–acetylene, catalyzed by copper(I) chloride and succinic acid as an additive, in good to excellent yields. This method is advantageous in that desilylation of the trimethylsilyl selenium–acetylene occurs in situ. The reaction time was monitored by FTIR studies and a probable mechanism is described. Scale-up was also performed in satisfactory yield. These selenium propargylamines could be hydrohalogenated to synthesize halovinyl selenides. The stereochemistry was determined by treatment with n-butyllithium and the coupling constant (J) values in 1H NMR spectra. The vinyl selenides were employed in Sonogashira cross-coupling reactions to produce the corresponding enynes, with yields ranging from moderate to good.

4-Organoselenium-quinolines were synthesized via model multi-component Povarov (MCR) reactions between p-anisidine, ethyl glyoxylate and ethynyl(phenyl)selane, catalyzed by the Lewis acid Yb(OTf)3, with yields ranging from moderate to good. This method is advantageous in that there is no requirement for an oxidant and that the reaction has a wide scope. These 4-organoselenium-quinolines allowed access to 4-alkynyl-quinolines, which were synthesized via copper free Sonogashira cross-coupling reactions catalyzed by a new palladium catalyst that employs an oxazoline derivative as a ligand. A plausible mechanism was proposed based on HRMS studies.

A new palladium catalyst system, generated in situ from palladium(II) chloride and hydroxynaphthalene-2-oxazolines as ligands, has been developed and used in Suzuki-Miyaura cross-coupling reactions with potassium heteroaryl- and aryltrifluoroborate salts to synthesize biphenyl derivatives in good to high yields. It was observed that the catalyst works only when generated in situ. When isolated the formation of a solid occurs which when subjected to x-ray diffraction shows that the palladium atom is bound to two oxazolines. The presence of electron donor or electron withdrawals groups does not significantly affect reaction performance. This allows easy preparation for use without the inconvenience of catalyst decomposition and need for storage care. A plausible mechanism reaction was suggested based on HRMS studies.

1,2,3-Triazol tyrosines were synthesized from tyrosine alkynes that were in turn prepared via Sonogashira cross-coupling reaction. The tyrosine alkynes were subjected to click-chemistry reaction conditions leading to the corresponding 3-(1,2,3-triazolyl)-tyrosines in yields ranging from moderate to good.