A multicomponent pharmacophore fragment-decoration approach to identify selective LRRK2-targeting probes

Tassini, Sabrina; Castagnolo, Daniele; Scalacci, Nicoló; Kiššová, Miroslava; Armijos-Rivera, Jorge I.; Giagnorio, Federica; Maga, Giovanni; Costantino, Gabriele; Crespan, Emmanuele; Radi, Marco

doi:10.1039/c5md00462d

Cited by 5 publications

(6 citation statements)

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“…All tyrosine- and serine/threonine kinase reactions were performed according to the manufacturer’s instructions, using 10–50 ng of enzyme. Details on the nature of the substrates and their concentration are reported elsewhere . For some kinases, NP-40 or BSA was added.…”

Section: Methodsmentioning

confidence: 99%

“…To account for variation in transfection efficiency the pHTomato fluorescence was normalized using average fluorescence intensity of a soluble eGFP, coexpressed in the cytosol. Because the rise in pHTomato fluorescence falls largely within the 6.5− 8.8 pH range, 63 the change in fluorescence obtained upon increasing extracellular pH (ΔF membrane ) was used as an estimate of membraneexposed CFTR.…”

Section: Ms (Esi) [M + H]mentioning

confidence: 99%

“…Details on the nature of the substrates and their concentration are reported elsewhere. 63 For some kinases, NP-40 or BSA was added. All reactions were performed in 10 μL at 30 °C for 10 min using protein low-binding tubes.…”

Section: ■ Associated Contentmentioning

confidence: 99%

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Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases

et al. 2017

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Enteroviruses (EVs) are among the most frequent infectious agents in humans worldwide and represent the leading cause of upper respiratory tract infections. No drugs for the treatment of EV infections are currently available. Recent studies have also linked EV infection with pulmonary exacerbations, especially in cystic fibrosis (CF) patients, and the importance of this link is probably underestimated. The aim of this work was to develop a new class of multitarget agents active both as broad-spectrum antivirals and as correctors of the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) folding defect responsible for >90% of CF cases. We report herein the discovery of the first small molecules able to simultaneously act as correctors of the F508del-CFTR folding defect and as broad-spectrum antivirals against a panel of EVs representative of all major species.

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Section: Methodsmentioning

confidence: 99%

Section: Ms (Esi) [M + H]mentioning

confidence: 99%

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Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases

et al. 2017

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“…[25][26]29 Such characteristics are not particularly suitable for libraries generation in hit/drug discovery campaigns: the ideal synthetic approach should be fast, versatile, time and step economic and should be suitable, as far as possible, for combinatorial and parallel chemistry applications. 35 As a continuation of our interest in the development of microwave-assisted and multicomponent strategies for the synthesis of biologically active probes, [36][37][38] we wanted to develop a new microwave-assisted procedure for the synthesis of substituted benzofurans in a one-pot fashion, since an efficient multicomponent approach to the synthesis of the benzofurans is still elusive. We report herein the first microwaveassisted one-pot three-component catalyst-free procedure for the synthesis of highly functionalized benzofuran-2-carboxamides directly from commercially available building blocks in extremely short reaction times.…”

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confidence: 99%

“…

Radi, M. (2016). A microwave-assisted multicomponent protocol for the synthesis of benzofuran-2-carboxamides.

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A microwave-assisted multicomponent protocol for the synthesis of benzofuran-2-carboxamides

Vincetti

Brianza

Scalacci

et al. 2016

Tetrahedron Letters

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Radi, M. (2016). A microwave-assisted multicomponent protocol for the synthesis of benzofuran-2-carboxamides. TETRAHEDRON LETTERS. DOI: 10.1016DOI: 10. /j.tetlet.2016 Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rightsCopyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights.•Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research.•You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policyIf you believe that this document breaches copyright please contact librarypure@kcl.ac.uk providing details, and we will remove access to the work immediately and investigate your claim.

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A Microwave‐Assisted One‐Pot Three‐Step Metal‐Free [4+2] Annulation for the Sustainable Synthesis of Highly Substituted 1,2,4‐Triazines

Rubini,

Grazia Martina,

Incerti

et al. 2024

Eur J Org Chem

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Herein we report the first microwave‐assisted one‐pot three‐step metal‐free [4+2] procedure for the synthesis of 5,6‐substituted‐3‐hydrazinyl‐1,2,4‐triazines directly from commercially available aromatic and heteroaromatic ketones. The 3‐hydrazinyl‐1,2,4‐triazine can be isolated or further elaborated, after a simple work‐up, by direct condensation with different aldehydes or ketones to provide highly functionalized hydrazone‐derivatives. This protocol represents a rapid, efficient, and sustainable approach for the development of new highly functionalized 1,2,4‐triazine derivatives with potential biological interest.

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A multicomponent pharmacophore fragment-decoration approach to identify selective LRRK2-targeting probes

Abstract: Herein we report the development of a new versatile chemical tool for the rapid identification of LRRK2-targeting probes as potential anti-Parkinson's agents.

Cited by 5 publications

References 50 publications

Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases

Discovery of Multitarget Agents Active as Broad-Spectrum Antivirals and Correctors of Cystic Fibrosis Transmembrane Conductance Regulator for Associated Pulmonary Diseases

A microwave-assisted multicomponent protocol for the synthesis of benzofuran-2-carboxamides

A Microwave‐Assisted One‐Pot Three‐Step Metal‐Free [4+2] Annulation for the Sustainable Synthesis of Highly Substituted 1,2,4‐Triazines

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