Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid

Corredor, Miriam; Bujons, Jordi; Orzáez, Mar; Sancho, Mónica; Pérez‐Payá, Enrique; Alfonso, Ignacio; Messeguer, Àngel

doi:10.1016/j.ejmech.2013.03.004

Cited by 19 publications

(17 citation statements)

References 36 publications

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“…A diverse set of 1,5-triazole products can be found in these reports which cover a wide range of targets and target classes including various enzyme inhibitors, [203][204][205][206][207][208][209][210][211][212][213] kinases, [214][215][216][217] proteases, 110,112 antivirals 218 (see also chapter 5.3) G-protein coupled receptors (GPCRs), 219 ion channels, [220][221][222] heat shock proteins, 95 and tRNA ligands. 223 1,5-Triazole derivatives have shown activity against numerous cancer cell lines, 205,215,[224][225][226][227] and against the parasites Trypanosoma cruzi 70,228 and Plasmodium falciparum.…”

Section: Target-oriented Medicinal Chemistrymentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years. CONTENTS

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Section: Target-oriented Medicinal Chemistrymentioning

confidence: 99%

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

et al. 2016

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“…Most of the starting materials ( 6 , 7 , and 8 a–e ) are commercially available. However, the triazole aldehyde 9 bearing the 2,4‐dichlorophenetyl moiety had to be prepared as previously reported . No substantial differences in the reaction yields were observed when performing the Ugi‐4CC, obtaining values from 60 to 76 % with the different amines (Table ).…”

Section: Resultsmentioning

confidence: 90%

“…The Ugi‐4CC requires a high concentration in the mixture and a specific order of addition. From our previous work, we established that the imine formation is completed after 6 h and, afterward, the addition of the isocyanide and the carboxylic acid must be done within 30 min to avoid imine hydrolysis. The key reaction for β‐lactam ring formation was a base‐promoted intramolecular cyclization (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…However,t he triazole aldehyde 9 bearing the 2,4-dichlorophenetyl moiety had to be prepared as previously reported. [19] No substantiald ifferences in the reaction yields were observed when performing the Ugi-4CC, obtaining values from 60 to 76 %w ith the different amines (Table 1). Thiss tep is essential to intro-duce variability at R 3 in the library of b-lactams,a nd the robustnesso ft he reactionw as highly useful.T he Ugi-4CCr equires ah igh concentration in the mixture and as pecific order of addition.…”

Section: Regioselective Synthesis Of B-lactams3mentioning

confidence: 95%

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Regioselective Synthesis of a Family of β‐Lactams Bearing a Triazole Moiety as Potential Apoptosis Inhibitors

et al. 2016

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Apoptosis is a biological process important to several human diseases; it is strongly regulated through protein–protein interactions and complex formation. We previously reported the synthesis of apoptosis inhibitors bearing an exocyclic triazole amide isoster by using an Ugi four‐component coupling reaction (Ugi‐4CC), followed by a base‐promoted intramolecular cyclization. Depending on the substitution patterns and the reaction conditions, this cyclization forms the six‐ or four‐membered ring. Two compounds bearing the β‐lactam scaffold turned out to be the most potent inhibitors. This encouraged us to optimize the modulation of the cyclization, and prepare a library of 15 β‐lactams with total regioselectivity. Moreover, we aimed to improve the bioavailability of these compounds through the introduction of diversity at different substitution positions. The activity of these compounds as apoptosis inhibitors in cellular extracts has been evaluated, showing an increase in their potency.

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“…Such antagonism impairs mitochondrial-mediated apoptosis, which is associated with many neurodegenerative diseases 42 . Introducing conformational constraint 43 and conjugation of the peptoid to cell penetrating peptides 44 or a polymeric carrier 45 enhance the effectiveness of these peptoids. Thus, peptoids can target neuroprotective pathways relevant to neurodegenerative diseases.…”

Section: Peptoids As Neuroprotective Agentsmentioning

confidence: 99%

Peptoids: Emerging Therapeutics for Neurodegeneration

Moss¹

2017

J Neurol Neuromedicine

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In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti-inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.

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Optimizing the control of apoptosis by amide/triazole isosteric substitution in a constrained peptoid

Cited by 19 publications

References 36 publications

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

Regioselective Synthesis of a Family of β‐Lactams Bearing a Triazole Moiety as Potential Apoptosis Inhibitors

Peptoids: Emerging Therapeutics for Neurodegeneration

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