A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities

• Published in: European journal of medicinal chemistry Vol. 213; pp. 113052 - 113064
• Main Authors: Mailahn, Daniela H., Iarocz, Lucas E.B., Nobre, Patrick C., Perin, Gelson, Sinott, Airton, Pesarico, Ana Paula, Birmann, Paloma T., Savegnago, Lucielli, Silva, Márcio S.
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 05.03.2021; Elsevier
• Subjects: Animals; Antioxidants - chemical synthesis; Antioxidants - pharmacology; Biomarkers - blood; Brain; Chalcogens - chemistry; Chemistry, Medicinal; Drug Evaluation, Preclinical; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - pharmacology; Free Radicals - metabolism; Glutathione Peroxidase - metabolism; Green Chemistry Technology - methods; Humans; Kidney; Life Sciences & Biomedicine; Liver; Male; Mice; Organophosphonates - chemical synthesis; Organophosphonates - pharmacology; Oxidation-Reduction; Pharmacology & Pharmacy; Science & Technology; Selenium Compounds - chemistry; Solvents - chemistry; Structure-Activity Relationship; Superoxide Dismutase - metabolism; Tellurium - chemistry
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2020.113052

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50 °C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe = 866.0 ppm), 125Te{1H} (δTe = 422.0 ppm) and 31P{1H} (δP = −1.0, −13.0 and −15.0 ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened in vitro and ex vivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases. [Display omitted] •Synthesis of phosphorochalcogenoates under mild conditions, where neither catalyst nor additive is required.•Broad substrate scope, including phosphorochalcogenoates containing tellurium element.•Stability study demonstrated that some phosphorochalcogenoates are unstable, crediting the biological results.•Phosphorochalcogenoates have shown antioxidant propriety, acting against oxidative stress in biological systems.