New Phosphoramidates Containing Selenium as Leishmanicidal Agents
| Autor: | Carlos Aydillo, Daniel Plano, Carmen Sanmartín, Esther Moreno, Juan Carlos García Soriano, Mikel Etxebeste-Mitxeltorena, Antonio Jiménez-Ruiz, Socorro Espuelas |
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| Rok vydání: | 2021 |
| Předmět: |
Leishmania
Pharmacology Chemistry Antiprotozoal Agents Trypanothione chemistry.chemical_element Phosphoramidate Biosynthesis Mass spectrometry Amides Combinatorial chemistry Redox In vitro Selenium chemistry.chemical_compound Infectious Diseases Pharmaceutical Preparations Elemental analysis Phosphoric Acids Pharmacology (medical) Fourier transform infrared spectroscopy |
| Zdroj: | Antimicrob Agents Chemother |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00590-21 |
| Popis: | This work reports the synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), (1)H, (13)C, and (79)Se nuclear magnetic resonance (NMR), mass spectrometry, and elemental analysis techniques as well as the in vitro evaluation of the leishmanicidal activity of 13 new selenophosphoramidate derivatives. Among the new compounds, four of them (compounds 1f, 1g, 2f, and 2g), which exhibited the best profiles, were tested against infected macrophages and were selected for further studies related to their leishmanicidal mechanism. In this regard, trypanothione redox system alteration was determined. Compound 1g, under similar conditions, was more effective than the corresponding references. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that selenophosphoramidate functionalities may represent a scaffold to be explored toward the development of new agents for leishmania treatment. |
| Databáze: | OpenAIRE |
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