Synthesis, characterization, synergistic antimicrobial properties and molecular docking of sugar modified uridine derivatives

Abstract

Nucleosides and their analogues are an important, well-established class of clinically useful medicinal agents that exhibit antiviral and anticancer activity. Thus, our research group has focused on the synthesis of new nucleoside derivatives that could be tested for their broad-spectrum biological activity. In this study, two new series of nucleoside derivatives were synthesized from uridine (1) through facile two-step reactions using the direct acylation method, affording 5’-O-acyl uridine derivatives in good yields. The isolated uridine analogs were further transformed into two series of 2’,3’-di-O-acyl derivatives bearing a wide variety of functionalities in a single molecular framework to evaluate their antimicrobial activity. The new synthesized compounds were characterized through physicochemical, elemental and spectroscopic analysis, and all were screened for their in vitro antimicrobial activity against selected human and plant pathogenic strains. The test compounds revealed moderate to good antibacterial and antifungal activities and were more effective against fungal phytopathogens than against bacterial strains, while many of them exhibited better antimicrobial activity than standard antibiotics. Minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) tests against all microorganisms were also conducted for five compounds based on their activity (6, 11, 13, 16, and 17). In addition, all the derivatives were optimized using density functional theory (DFT) B3LYP/6-31g+(d,p) calculations to elucidate their thermal and molecular orbital properties. A molecular docking study was performed using the human protein 5WS1 to predict their binding affinity and modes, and ADMET and SwissADME calculations confirmed the improved pharmacokinetic properties of the compounds. Besides, structure–activity relationship (SAR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) studies were also performed. Thus, the improvement of the bioactivity of these compounds is expected to significantly contribute to the design of more antimicrobial agents for therapeutic use in the future.

Synthesis, Antimicrobial, Anticancer, PASS, Molecular Docking, Molecular Dynamic Simulations & Pharmacokinetic Predictions of Some Methyl β-D-Galactopyranoside Analogs

“…They are the source of the metabolic energy supply and the fine-tuning of cell-cell interactions and other crucial processes [3,4]. It was found from the literature survey that a large number of biologically active compounds also possess aromatic, heteroaromatic, and acyl substituents [5][6][7][8][9][10][11][12]. For example, the benzene substituted benzene, and nitrogen, sulfur, and halogen-containing substituents are known to enhance the biological activity of the parent compound [13][14][15][16].…”

Methyl β-D-galactopyranoside esters as potential inhibitors for SARS-CoV-2 protease enzyme: synthesis, antimicrobial, PASS, molecular docking, molecular dynamics simulations and quantum computations

“…Next, the contents of the wells were seeded on Müeller-Hinton agar plates to determine the MBC, which is the lowest concentration that kills bacteria. The broth microdilution method was used to calculate the MIC and MBC [11].…”

“…According to a literature review, many biologically active compounds have aromatic, heteroaromatic, and acyl substituents [5][6][7][8][9][10][11][12]. For example, benzene, substituted benzene, nitrogen, sulfur, and halogen-containing substituents are known to improve the biological activity of the parent compound [13][14][15][16].…”

PASS prediction, molecular docking and pharmacokinetic studies of acyl substituted bioactive galactopyranoside esters as antibacterial agents

“…[18][19][20][21] It is also known that if an active nucleus is linked to another active nucleus the resulting molecule may possess greater potential for biological activity. [22][23][24][25][26] Moreover, selective acylation of carbohydrates and evaluation of microbial activities reveal that in many cases the combination of two or more heteroaromatic nuclei and acyl groups enhances the biological activity manifold over its parent nucleus. In a recent study, some methyl-β-D-galactopyranoside (MDG) esters are found to be potential inhibitors against cancer cell protein [ADP-ribose] polymerase1.…”