Heterocycles in Peptidomimetics and Pseudopeptides: Design and Synthesis

Cerminara, Iole; Chiummiento, Lucia; Funicello, Maria; Guarnaccio, Ambra; Lupattelli, Paolo

doi:10.3390/ph5030297

Cited by 22 publications

(11 citation statements)

References 57 publications

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“…In our experience of the synthesis of highly functionalized small molecules with aryl and heteroaryl structures [10][11][12], we evidenced the crucial effect of the presence of heterocyclic moiety in PIs structure, either in the core of the inhibitors [13][14][15] or in the P2 position [16][17][18].…”

Section: Introductionmentioning

confidence: 92%

The Pseudo-Symmetric N-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation

et al. 2021

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Here, we report the synthesis, enzyme inhibition and structure–activity relationship studies of a new potent class of HIV-1 protease inhibitors, which contain a pseudo-symmetric hydroxyethylamine core and heteroarylcarboxyamide moieties. The simple synthetic pathway furnished nine compounds in a few steps with high yields. The compounds were designed taking into account our previous results on other series of inhibitors with different substituents at P’ and P’’ and different ways of linking them to the inhibitor core. Potent inhibitory activity was obtained with nanomolar IC50 values measured with a standard fluorimetric test in 100 mM MES buffer, pH 5.5, containing 400 mM NaCl, 1 mM EDTA, 1 mM DTT and 1 mg/ml BSA. Compounds 9a–c, containing the indole ring in P1, exhibited an HIV-1 protease inhibitory activity more powerful than darunavir in the same assay. To obtain molecular insight into the binding properties of these compounds, docking analysis was performed, and their binding properties were also compared.

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Section: Introductionmentioning

confidence: 92%

The Pseudo-Symmetric N-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation

et al. 2021

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“…The contribution of applied green chemistry is based on the transfer of basic improvement from main stream researches [ 12 – 31 ] to production processes in primary sector.…”

Section: Final Considerationsmentioning

confidence: 99%

Green Chemistry, Circular Economy and Sustainable Development: An Operational Perspective to Scale Research Results in SMEs Practices

Cerminara

Chiummiento

Funicello

et al. 2020

Computational Science and Its Applications – ICCSA 2020

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Green Chemistry, Circular Economy and Sustainability are issues at the center of the modern scientific debate and three major trends in the global market. These three subjects are interconnected and interdependent and represent an affordable set of principles bringing innovations in the management of complex processes connected with anthropic use of resources. Today’s world population requires more natural resources be consumed than in previous decades, thus contributing to making primary resources increasingly scarce and with limited access. Furthermore, an issue that persisted over time to become unsustainable is the waste emergency. It is also linked to the low capacity of operators to recover and re-use scraps of the production processes losing production values and generating environmental pressure. Companies, whose growth is crucial for the economic system, generate waste in all stages of the production processes; although there is an increasing attention and awareness on the issue of waste, we are still in the early stages of the process that will lead SMEs to zero waste production. If we recognize such attribute as a competitive factor, we can identify in advance a critical innovation demand generated by SMEs operating in low competitive areas which has to be supported with technological transfer inn order to result “green” and effective in the short/medium term. This paper presents data and defines there critical innovations domain in order to deliver an effective and scalable innovation transfer concerning circular economy thorough the application of green chemistry principles exploiting territorial factors in order to deliver sustainable local production chains.

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“…Moreover, peptides are generally highly flexible; this feature decreases their ability to adopt a specific bioactive conformation and hampers their biological activity. The introduction of heterocyclic cores into peptides increases their structural rigidity and potentially restricts their structures into the bioactive conformation, provided that both the s ‐ cis and s ‐ trans conformation of the peptide bond can be easily mimicked.…”

Section: Introductionmentioning

confidence: 99%

Regioselective Solid‐Phase Synthesis of Peptide Analogues Containing 3,4‐ or 3,5‐Disubstituted Isoxazole as s‐cis or s‐trans Peptide Bond Mimics

2019

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A method for regioselective solid‐phase synthesis of disubstituted peptidoisoxazoles is reported. Improved conditions for the synthesis of 3,5‐disubstituted isoxazoles (mimicking s‐trans peptide bond) without metal catalysts were implemented. New conditions enabling the synthesis of 3,4‐disubstituted isoxazoles (mimicking s‐cis peptide bond) using ruthenium catalysts were developed. This study provides a means for the regioselective preparation of new libraries of peptidomimetic molecules containing an isoxazole moiety within the backbone.

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Heterocycles in Peptidomimetics and Pseudopeptides: Design and Synthesis

Abstract: This minireview provides a brief outline of the peculiar aspects of the preparation of peptidomimetic and pseudopeptidic structures containing heterocycles. In particular novel tricyclic structures are investigated as potential drugs.

Cited by 22 publications

References 57 publications

The Pseudo-Symmetric N-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation

The Pseudo-Symmetric N-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation

Green Chemistry, Circular Economy and Sustainable Development: An Operational Perspective to Scale Research Results in SMEs Practices

Regioselective Solid‐Phase Synthesis of Peptide Analogues Containing 3,4‐ or 3,5‐Disubstituted Isoxazole as s‐cis or s‐trans Peptide Bond Mimics

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