New Phosphoramidates Containing Selenium as Leishmanicidal Agents

• Published in: Antimicrobial agents and chemotherapy 2021-09, Vol.65 (10), p.e0059021-e0059021
• Main Authors: Etxebeste-Mitxeltorena, Mikel, Plano, Daniel, Espuelas, Socorro, Moreno, Esther, Aydillo, Carlos, Jiménez-Ruiz, Antonio, García Soriano, Juan Carlos, Sanmartín, Carmen
• Format: Article
• Language: English
• Subjects: Amides; Antimicrobial Chemotherapy; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Biosynthesis; Chemistry; Chemistry; Biosynthesis; Leishmania; Pharmaceutical Preparations; Phosphoric Acids; Selenium - pharmacology
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.00590-21

This work reports the synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), H, C, and Se nuclear magnetic resonance (NMR), mass spectrometry, and elemental analysis techniques as well as the 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.