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11.
Lissy Z. F. Gross Mariana Sacerdoti Prof. Albrecht Piiper Prof. Stefan Zeuzem Dr. Alejandro E. Leroux Dr. Ricardo M. Biondi 《ChemMedChem》2020,15(18):1682-1690
Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein. 相似文献
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Lydia Saidi Dr. Djenisa H. A. Rocha Dr. Oualid Talhi Dr. Yamina Bentarzi Prof. Dr. Bellara Nedjar-Kolli Dr. Khaldoun Bachari Dr. Filipe A. Almeida Paz Dr. Luisa A. Helguero Prof. Dr. Artur M. S. Silva 《ChemMedChem》2019,14(10):1041-1048
Breast and prostate cancers are frequently treated with chemotherapy. Several novel chemicals are being reported for this purpose, particularly synthetic and natural benzophenones. This work reports the synthesis of substituted 2-hydroxybenzophenones through 1,4-conjugate addition/intramolecular cycloaddition/dehydration of nitromethane on key intermediate chromones. Structures were extensively studied by means of 2D NMR spectroscopy and single-crystal XRD. Their cytotoxicity was evaluated in vitro in two breast cancer cell lines (MDA-MB-231 and T47-D) and one prostate cancer cell line (PC3). The most potent compound exhibited good cytotoxic effects against the three cancer cell lines (IC50 values ranging from 12.09 to 26.49 μm ) and induced cell-cycle retardation only on prostate cancer cells, which suggested that it might exert cell-type-specific effects. 相似文献
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Ricardo Cambraia Parreira Diana Paola Gmez‐Mendoza Itamar Couto Guedes de Jesus Rafael Pereira Lemos Anderson Kennedy Santos Cristiana Perdigo Rezende Henrique Csar Pereira Figueiredo Mauro Cunha Xavier Pinto Frank Kjeldsen Silvia Guatimosim Rodrigo Ribeiro Resende Thiago Verano‐Braga 《Proteomics. Clinical applications》2020,14(4)
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Caio Felippe Curitiba Marcellos Camila M. Senna Figueiredo Frederico W. Tavares Maurício Bezerra de Souza Jr. Paulo Laranjeira da Cunha Lage João Francisco Cajaiba da Silva Argimiro R. Secchi Amaro G. Barreto Jr. 《加拿大化工杂志》2020,98(11):2435-2450
An experimental methodology for inferring brine dissolution rate in monoethylene glycol (MEG) solutions at different temperatures using a webcam combined with a mathematical model is presented. The measurement system is designed to track the RGB (red, green, and blue) colour variations during the dissolution process. A dynamic model augmented with the population balance equation is applied to describe the dissolution process. Moreover, the dissolution rate is consistently related to the temperature and MEG concentration through the driving force based on the Gibbs energy and chemical affinity. The applied low-cost measurement apparatus proved to be a useful resource for tracking the dissolution dynamics in a wide range of undersaturation. 相似文献
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L.C. Souza A.C.A. Silva N.O. Dantas P.C. Morais S.W. da Silva 《Ceramics International》2018,44(1):208-215
Successful fabrication of glass-based hybrid nanocomposites (GHNCs) incorporating Ag, core-shell CdSe/CdS and CdSxSe1?x nanoparticles (NPs) is herein reported. Both metallic (Ag) and semiconductor (CdSe/CdS) NPs were pre-synthesized, suspended in colloids and added into the sol-gel reaction medium which was used to fabricate the GHNCs. During fabrication of the nanocomposites a fraction (20–60%) of core-shell CdSe/CdS NPs was alloyed into CdSxSe1?x (0.20 < x < 0.35) NPs without changing morphology. Modulation of in situ alloying is possible via the relative content of organics added into the sol-gel protocol. Within colloids Ag (core-shell CdSe/CdS) NPs presented average diameter and polydispersity index of 49.5 nm (4.2 nm) and 0.41 (0.21), respectively. On the other hand, the Ag (core-shell CdSe/CdS) NPs’ average diameter and polydispersity index assessed from the GHNCs were respectively 51.5 nm (4.1 nm) and 0.43 (0.25), revealing negligible aggregation of the nanophases within the glass template. The new GHNCs herein introduced presented two independent excitonic transitions associated to homogenously dispersed semiconductor NPs, peaking around 420 nm (core-shell CdSe/CdS) and 650 nm (CdSxSe1?x) and matching the plasmonic resonance (Ag NPs) in the 400–500 nm range. We envisage that the new GHNCs represent very promising candidates for superior light manipulation while illuminated with multiple laser beams in quantum interference-based devices. 相似文献
19.
Erika Aparecida Silveira Golnaz Vaseghi Annelisa Silva de Carvalho Santos Nathalie Kliemann Farzad Masoudkabir Matias Noll Noushin Mohammadifard Nizal Sarrafzadegan Cesar de Oliveira 《International journal of molecular sciences》2020,21(23)
The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT’s role and ways to manage or prevent it are needed. 相似文献
20.
Ricardo Martínez-Corona Gerardo Vázquez Marrufo Carlos Cortés Penagos Luis Alberto Madrigal-Pérez Juan Carlos González-Hernández 《Yeast (Chichester, England)》2020,37(1):149-162
Lipases are hydrolytic enzymes that break the ester bonds of triglycerides, generating free fatty acids and glycerol. Extracellular lipase activity has been reported for the nonconventional yeast Kluyveromyces marxianus, grown in olive oil as a substrate, and the presence of at least eight putative lipases has been detected in its genome. However, to date, there is no experimental evidence on the physiological role of the putative lipases nor their structural and catalytic properties. In this study, a bioinformatic analysis of the genes of the putative lipases from K. marxianus L-2029 was performed, particularly identifying and characterizing the extracellular expected enzymes, due to their biotechnological relevance. The amino acid sequence of 10 putative lipases, obtained by in silico translation, ranged between 389 and 773 amino acids. Two of the analysed putative proteins showed a signal peptide, 25 and 33 amino acids long for KmYJR107Wp and KmLIP3p, and a molecular weight of 44.53 and 58.23 kDa, respectively. The amino acid alignment of KmLIP3p and KmYJR107Wp with the crystallized lipases from a patatin and the YlLip2 lipase from Yarrowia lipolytica, respectively, revealed the presence of the hydrolase characteristic motifs. From the 3D models of putative extracellular K. marxianus L-2029 lipases, the conserved pentapeptide of each was determined, being GTSMG for KmLIP3p and GHSLG for KmYJR107Wp; besides, the genes of these two enzymes (LIP3 and YJR107W) are apparently regulated by oleate response elements. The phylogenetic analysis of all K. marxianus lipases revealed evolutionary affinities with lipases from abH15.03, abH23.01, and abH23.02 families. 相似文献