Comprehensive Chemical Analysis of the Methyl 3-Nitrogen-2,3-Dideoxysaccharides Derivatives with d-ribo-Configuration: Synthesis, Reactivity of HIV-1 Reverse Transcriptase Inhibitors.

Abstract

This study extends previous research, particularly focusing on patented scientific objects No. ID: PL 240 353 B1, investigating the physicochemical properties of the methyl 3-azido- and 3-amino-2,3-dideoxysaccharides with a nucleoside scaffold similar to 3'-azidothymidine (AZT). The study utilizes multiwavelength spectrophotometric and potentiometric methods to evaluate the ionization of the saccharide units in aqueous solutions. pK_a values, obtained from two independent methods, reveal significant sugar ionization effects on UV spectra with varying pH levels. Stability constants for divalent metal ion complexes (Cu²⁺ and Ni²⁺) with the saccharide isomers indicate that complex stoichiometries and stabilities are highly dependent on the configuration of sugar ring substituents. Spectrophotometric results show a descending order of CT-DNA-binding affinity: BRNH₂OMe > BRN₃OMe > ARN₃OMe > ARNH₂OMe, suggesting varied interaction strengths. Molecular docking of models of synthesized O-glycosides confirmed their potential as reverse transcriptase inhibitors. Among the derivatives tested, the compound BRN₃OMe displays the highest interaction with the enzyme active site residues and DNA, suggesting it may possess the greatest efficacy. Our reported results highlight the promising inhibitory properties of novel O-glycosides against HIV reverse transcriptase, supporting their potential development as antiviral agents.