On-resin synthesis of cyclic peptides via tandem N-to-S acyl migration and intramolecular thiol additive-free native chemical ligation

Serra, Gloria; Posada, Laura; Hojo, Hironobu

doi:10.1039/c9cc07783a

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…1) [35], as promising antimalarials with EC 50 values in the low micromolar or submicromolar range, respectively [36]. Considering these results, we decided to explore the "old" and versatile drug Ntz, its metabolite Tiz and bis-heterocycles analogs as part of a research program for the synthesis of potential antimalarials [37][38][39][40][41][42][43][44][45][46][47].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates

et al. 2022

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During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of "old" drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogs were prepared using two methodologies and evaluated against P. falciparum 3D7. A bithiazole analog, showed attractive inhibitory activity with an EC 50 value of 5.9 μM, low propensity to show toxic effect against HepG2 cells at 25 μM, and no cross-resistance with standard antimalarials.

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Section: Introductionmentioning

confidence: 99%

Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates

et al. 2022

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“…As part of a research program for the synthesis of potential antimalarials [37][38][39][40][41][42][43][44][45][46][47], in this work, we present the synthesis and biological evaluation against P. falciparum 3 D7 of Ntz, Tiz and 2-aminothiazole analogues, Figure 2. Compounds of A series do not present the nitro substituent in the thiazole ring in order to study the in uence of that group in the antimalarial activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis And Antiplasmodial Assessment of Nitazoxanide And Analogues As New Antimalarial Candidates

Irabuena

Scarone

Souza

et al. 2021

Preprint

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During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modelling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of “old” drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogues were prepared using two methodologies and evaluated against P. falciparum 3 D7. A bithiazole analogue, showed attractive inhibitory activity with an EC50 value of 5.9 mM and low propensity to show toxic effect against HepG2 cells at 25 mM.

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“…NCL involves the preparation of an unprotected C-thioester peptide that allows reaction with an unprotected N-terminal Cys to render first the thioester involving the thiol of the Cys, which rearranges to form the natural amide bond (Figure 1). This technique has allowed the synthesis of difficult, large peptides, and proteins (Camarero and Muir, 1999;Camarero et al, 2001;Miller et al, 2003;Avital-Shmilovici et al, 2013;Okamoto et al, 2014a,b;Boll et al, 2015;Pala-Pujadas et al, 2018;Snella et al, 2018;Spengler et al, 2018;Ashhurst et al, 2019;Sun and Brik, 2019;Jbara et al, 2020;Serra et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Solid-Phase Synthesis of Head to Side-Chain Tyr-Cyclodepsipeptides Through a Cyclative Cleavage From Fmoc-MeDbz/MeNbz-resins

et al. 2020

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Cyclic depsipeptides constitute a fascinating class of natural products. Most of them are characterized by an ester formed between the β-hydroxy function of Ser/Thr-and related amino acids-and the carboxylic group of the C-terminal amino acid. Less frequent are those where the thiol of Cys is involved rendering a thioester (cyclo thiodepsipeptides) and even less common are the cyclo depsipeptides with a phenyl ester coming from the side-chain of Tyr. Herein, the preparation of the later through a cyclative cleavage using the Fmoc-MeDbz/MeNbz-resin is described. This resin has previously reported for the synthesis of cyclo thiodepsipeptides and homodetic peptides. The use of that resin for the preparation of all these peptides is also summarized.

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On-resin synthesis of cyclic peptides via tandem N-to-S acyl migration and intramolecular thiol additive-free native chemical ligation

Abstract: A novel methodology for the synthesis of cyclic peptides by on-resin intramolecular native chemical ligation (NCL) assisted by N-ethylcysteine using Fmoc/SPPS is described.

Cited by 13 publications

References 31 publications

Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates

Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates

Synthesis And Antiplasmodial Assessment of Nitazoxanide And Analogues As New Antimalarial Candidates

Solid-Phase Synthesis of Head to Side-Chain Tyr-Cyclodepsipeptides Through a Cyclative Cleavage From Fmoc-MeDbz/MeNbz-resins

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