作者:
Lu, JianiHe, YingyingLi, YaqiChen, XixiangLi, HongtaoChen, xuwenXu, JianrongChen, HongzhuanWang, YingHe, xiaoLiu, ShunyingChen, LiliShanghai Univ Tradit Chinese Med
Longhua Hosp Inst Interdisciplinary Integrat Med Res Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China East China Normal Univ
Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev Sch Chem & Mol Engn Shanghai 200062 Peoples R China Hunan Normal Univ
Coll Life Sci Natl & Local Joint Engn Lab Anim Peptide Drug Dev Changsha 410081 Peoples R China Hunan Normal Univ
Inst Interdisciplinary Studies Changsha 410081 Peoples R China Hunan Normal Univ
Furong Lab Peptide& Small Mol Drug R&D Plateform Changsha 410081 Hunan Peoples R China DP Technol
Beijing 100080 Peoples R China Shanghai Univ Tradit Chinese Med
Inst Interdisciplinary Integrat Med Res Acad Integrat Med Shanghai Frontiers Sci Ctr TCM Chem Biol Shanghai 201203 Peoples R China Shanghai Univ Tradit Chinese Med
Shanghai Inst Infect Dis & Biosecur Inst Interdisciplinary Integrat Med Res Res Ctr Tradit Chinese MedShanghai Frontiers Sci Shanghai 201203 Peoples R China East China Normal Univ
Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev Shanghai Frontiers Sci Ctr Mol Intelligent Synth Sch Chem & Mol Engn Shanghai 200062 Peoples R China NYU Shanghai
NYU East China Normal Univ Ctr Computat Chem Shanghai 200062 Peoples R China
As new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, they raise increasing concerns about the efficacy of neutralizing antibodies and vaccines. This situation undersc...
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As new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, they raise increasing concerns about the efficacy of neutralizing antibodies and vaccines. This situation underscores the urgent need for specific drugs against the coronavirus disease 2019 (COVID-19). Given that COVID-19 is particularly associated with substantial inflammation, the development of novel, effective antiviral and antiinflammatory agents represents a promising research direction. In this study, we virtually screened a library consisting of 2900 anti-inflammatory small molecules for their inhibitory effects on the 3-chymotrypsin-like protease (3CLpro) of SARS-CoV-2 and selected 23 promising candidates for further testing using a fluorescence resonance energy transfer (FRET) assay. The results indicated that Gnetol had the most potent inhibitory effect against SARS-CoV-2 3CLpro. Further structural modifications led to the identification of compounds 38 and 39, which displayed superior inhibitory activity. Compound 39 showed good selectivity for host proteases. Subsequently, Gnetol and its structural analogs, which demonstrated SARS-CoV-2 3CLpro inhibitory activity, were tested for their anti-inflammatory effects. Among these, Piceatannol and compound 39 exhibited enhanced antiinflammatory effects, with compound 39 alone showing the most potent antiviral and anti-inflammatory activity. Thus, our study has explored a new research strategy for discovering antiviral and anti-inflammatory bifunctional molecules. The discovery of Gnetol and its structural analogs has provided new lead candidates for the development of COVID-19 therapeutics.
Vinyl-substituted N-heterocycles, as more challenginginert olefinswith more stable reactivity, have brought about widespread attentionin the reaction of aza-Michael addition or reduction coupling ***, we report a [Pd-...
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Vinyl-substituted N-heterocycles, as more challenginginert olefinswith more stable reactivity, have brought about widespread attentionin the reaction of aza-Michael addition or reduction coupling ***, we report a [Pd-(eta(3)-C3H5)-Cl](2)/Sc-(OTf)(3)-catalyzed catalytic processaccelerated by Bronsted acids with a beta-selective aza-Michaeladdition to yield a gamma-quaternary carbon from vinyl-substitutedquinolines, diazos, and anilines/alcohols in one pot. The generationof anhydride analogues from Bronsted acid and the counter anion(OTf-) of Lewis acid promotes the activation ofthe corresponding Lewis acid and the nearly quantitative *** pi-cation and coordination interactions play pivotal rolesin the activation of the vinyl-quinoline substrates by the activatedLewis acid Sc-(OTf)(3). The control mechanistic evidence andDFT calculations presented a Pd/Sc/Bronsted acid co-catalyzedaddition mechanism. The triple co-catalytic system provides a strategyfor the activation of vinyl-quinolines with a linear selectivity containing gamma-quaternary carbon, and the developed method shows a broadsubstrate scope varying from alkyl/aryl alcohols and amines whichprovides a general and rapid strategy for the quinoline-based diverselibrary construction.
We have systematically investigated the electronic properties of Si doping germanene under external electric fields by the first-principle calculations. The results show that a wide range of linearly tunable and sizab...
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Ru(ii)-based photoactivated chemotherapy (PACT) agents are promising;however, their short wavelength absorption (generally <550 nm) and poor tumor accumulation ability limit their in vivo applications. Herein, bovi...
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Ru(ii)-based photoactivated chemotherapy (PACT) agents are promising;however, their short wavelength absorption (generally <550 nm) and poor tumor accumulation ability limit their in vivo applications. Herein, bovine serum albumin (BSA) coated lanthanide-doped upconversion nanoparticles (NaYF4:Yb:Tm@NaYF4 (UCNPs)) were loaded with a Ru(ii) PACT agent, i.e. [Ru(dip)(2)(spc)](+) (dip = 4,7-diphenyl-1,10-phenanthroline;spc = 2-sulfonic acid pyridine-3-carboxylic acid). The resultant UCNP@BSA@Ru can transfer [Ru(dip)(2)(spc)](+) to tumor cells in vitro as well as tumor tissues in vivo highly efficiently and selectively owing to the targeting ability of BSA and the enhanced permeability and retention effect of the nanoparticles. The subsequent near infrared (NIR) light irradiation at 980 nm or visible light irradiation at 470 nm can initiate dissociation of the spc ligand, and the released Ru(ii) aqua compounds ([Ru(dip)(2)(H2O)(2)](2+)) may exert a potent cytotoxicity towards a series of cancer cells but a much weaker effect on the normal IOSE80 cells. The in vivo (mouse) results showed that UCNP@BSA@Ru could inhibit tumor growth upon 980 nm irradiation more efficiently than in the dark and more efficiently than cisplatin (in the dark).
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