4897-84-1Relevant articles and documents
Synthesis of long-wavelength absorbing porphyrin m-benzoic acids as molecular tectons for surface studies
Meindl, Alina,Ryan, Aoife A.,Flanagan, Keith J.,Senge, Mathias O.
, p. 1518 - 1541 (2017)
Porphyrins are becoming increasingly important building blocks in material science. This is due in part to several favorable characteristics; such as strong absorption into the infrared region, tunable electronic properties and the possibility to modify and define the porphyrin core in multiple ways. Herein we report synthetic methodologies for porphyrin-based molecular tectons for surface studies. The study aims to generate porphyrins with directional anchoring groups of different length and we report a library of long-wavelength absorbing porphyrins with a special focus on organometallic coupling reactions for the introduction of benzoic acid moieties as anchor groups.
Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors
Campiani, Giuseppe,Cavella, Caterina,Osko, Jeremy D.,Brindisi, Margherita,Relitti, Nicola,Brogi, Simone,Saraswati, A. Prasanth,Federico, Stefano,Chemi, Giulia,Maramai, Samuele,Carullo, Gabriele,Jaeger, Benedikt,Carleo, Alfonso,Benedetti, Rosaria,Sarno, Federica,Lamponi, Stefania,Rottoli, Paola,Bargagli, Elena,Bertucci, Carlo,Tedesco, Daniele,Herp, Daniel,Senger, Johanna,Ruberti, Giovina,Saccoccia, Fulvio,Saponara, Simona,Gorelli, Beatrice,Valoti, Massimo,Kennedy, Breándan,Sundaramurthi, Husvinee,Butini, Stefania,Jung, Manfred,Roach, Katy M.,Altucci, Lucia,Bradding, Peter,Christianson, David W.,Gemma, Sandra,Prasse, Antje
, p. 9960 - 9988 (2021/07/31)
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novelhHDAC6 inhibitors, having low inhibitory potency overhHDAC1 andhHDAC8, as potential pharmacological tools for IPF treatment. Their inhibitory potency was combined with lowin vitroandin vivotoxicity. Structural analysis of 6h and structure-activity relationship studies contributed to the optimization of the binding mode of the new molecules. The best-performing analogues were tested for their efficacy in inhibiting fibrotic sphere formation and cell viability, proving their capability in reverting the IPF phenotype. The efficacy of analogue 6h was also determined in a validated human lung model of TGF-β1-dependent fibrogenesis. The results highlighted in this manuscript may pave the way for the identification of first-in-class molecules for the treatment of IPF.
C(alkenyl)-H Activation via Six-Membered Palladacycles: Catalytic 1,3-Diene Synthesis
Liu, Mingyu,Yang, Pusu,Karunananda, Malkanthi K.,Wang, Yanyan,Liu, Peng,Engle, Keary M.
supporting information, p. 5805 - 5813 (2018/05/14)
A catalytic method to prepare highly substituted 1,3-dienes from two different alkenes is described using a directed, palladium(II)-mediated C(alkenyl)-H activation strategy. The transformation exhibits broad scope across three synthetically useful substrate classes masked with suitable bidentate auxiliaries (4-pentenoic acids, allylic alcohols, and bishomoallylic amines) and tolerates internal nonconjugated alkenes, which have traditionally been a challenging class of substrates in this type of chemistry. Catalytic turnover is enabled by either MnO2 as the stoichiometric oxidant or co-catalytic Co(OAc)2 and O2 (1 atm). Experimental and computational studies were performed to elucidate the preference for C(alkenyl)-H activation over other potential pathways. As part of this effort, a structurally unique alkenylpalladium(II) dimer was isolated and characterized.
QSAR and molecular docking studies of the inhibitory activity of novel heterocyclic GABA analogues over GABA-AT
Rodríguez-Lozada, Josué,Tovar-Gudi?o, Erika,Guevara-Salazar, Juan Alberto,Razo-Hernández, Rodrigo Said,Santiago, ángel,Pastor, Nina,Fernández-Zertuche, Mario
, (2018/11/24)
We have previously reported the synthesis, in vitro and in silico activities of new GABA analogues as inhibitors of the GABA-AT enzyme from Pseudomonas fluorescens, where the nitrogen atom at the γ-position is embedded in heterocyclic scaffolds. With the goal of finding more potent inhibitors, we now report the synthesis of a new set of GABA analogues with a broader variation of heterocyclic scaffolds at the γ-position such as thiazolidines, methyl-substituted piperidines, morpholine and thiomorpholine and determined their inhibitory potential over the GABA-AT enzyme from Pseudomonas fluorescens. These structural modifications led to compound 9b which showed a 73% inhibition against this enzyme. In vivo studies with PTZ-induced seizures on male CD1 mice show that compound 9b has a neuroprotective effect at a 0.50 mmole/kg dose. A QSAR study was carried out to find the molecular descriptors associated with the structural changes in the GABA scaffold to explain their inhibitory activity against GABA-AT. Employing 3D molecular descriptors allowed us to propose the GABA analogues enantiomeric active form. To evaluate the interaction with Pseudomonas fluorescens and human GABA-AT by molecular docking, the constructions of homology models was carried out. From these calculations, 9b showed a strong interaction with both GABA-AT enzymes in agreement with experimental results and the QSAR model, which indicates that bulky ligands tend to be the better inhibitors especially those with a sulfur atom on their structure.
