One-Step Synthesis, Crystallography, and Acute Toxicity of Two Boron-Carbohydrate Adducts That Induce Sedation in Mice

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 6; p. 781
• Main Authors: Cordova-Chávez, Ricardo Ivan, Trujillo-Ferrara, José G, Padilla-Martínez, Itzia I, González-Espinosa, Héctor, Abad-García, Antonio, Farfán-García, Eunice D, Ortega-Camarillo, Clara, Contreras-Ramos, Alejandra, Soriano-Ursúa, Marvin A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.06.2024; MDPI
• Subjects: Acids; acute toxicity; adducts; Anesthesia; Biological activity; Boron; Brain cancer; carbohydrate; Carbohydrates; Crystallography; Drug dosages; Enzymes; Hypnosis; Kinases; Metabolism; neurons; Proteins; sedation; Toxicity; acute toxicity; adducts; boron; mice; neurons; sedation; carbohydrate
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17060781

Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD ) values by using Lorke's method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the β-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B-O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the C NMR spectra of both adducts. The acute toxicity tests showed that the LD value for both compounds was 1265 mg/kg, while the effective dose 50 (ED ) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications.