Synthesis, crystal structure, spectral analysis, DFT calculations, docking studies, in vitro biological activity evaluation and in silico drug-likeness prediction of a novel L-xylose derivative

Abstract

In this research, we have reported the synthesis and crystal structure analysis of compound 1, a novel xylose derivative functioning as a dual SGLT1/2 inhibitor. Compound 1 exhibited outstanding inhibitory activity against both SGLT1 (IC50=101.1 ± 0.4 nm) and SGLT2 (IC50=8.2 ± 0.2 nm). Consequently, compound 1 was selected for a comprehensive investigation into its molecular structural information and its interaction with SGLT1 and SGLT2. The structure of the compound 1 was characterized by X-ray diffraction, Mass spectrometry, 1H and 13C-NMR , FT-IR, FT-Raman and ECD spectroscopy. The conformations were optimized and the vibrational spectrum was predicted using density functional theory (DFT), and compared with the crystal structure and experimental data. Furthermore, MEP, RDG and ELF analyses were conducted to characterize the reaction sites susceptible to electrophilic and nucleophilic attacks. FMOs was used to evaluate the stability of the molecular structure. Subsequently, molecular docking studies were performed to investigate the interaction between SGLT1/2 and compound 1. The ADMET predictions indicate that compound 1 exhibits favorable druggability and pharmacokinetic properties