Uridine Derivatives as Potential Human Gene Protein Inhibitors | Chapter 5 | Chemistry and Biochemistry: Research Progress Vol. 8

 

Uridine (Urd) is a promising biochemical modulator to reduce host toxicity caused by 5-fluorouracil (5-FU) without impairing its antitumor activity. Elevated doses of Urd are required to achieve a protective effect against 5-FU toxicity, but exogenous administration of Urd is not well-tolerated. Selective inhibitors of human uridine phosphorylase (hUP) have been proposed as a strategy to increase Urd levels. Nucleosides and their analogues are well-known classes of clinically useful medicinal agents with antiviral and anticancer activities. In our study, two new series of nucleoside derivatives were synthesised from uridine (1) through a facile two-step reaction involving direct acylation, which afforded 5′-O-acyl uridine derivatives in reasonably good yields. These intermediates were further converted into two series of 2′,3′-di-O-acyl derivatives to evaluate their antimicrobial activity. The newly synthesised compounds were characterised by physicochemical, elemental, and spectroscopic analyses and subsequently tested in vitro against selected human and plant pathogenic strains. The results demonstrated moderate to good antibacterial and antifungal activities, with the compounds showing greater efficacy against fungal phytopathogens than bacterial strains. Notably, some compounds exhibited superior antimicrobial activity compared with standard antibiotics. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests were performed for five selected compounds (6, 11, 13, 16, and 17) based on their biological activity. Furthermore, all synthesised derivatives were optimised using density functional theory (DFT, B3LYP/3-21G) to predict their thermal stability and molecular orbital properties. Molecular docking studies were conducted using the human gene-encoded protein 5WS1 to evaluate their binding affinity and interaction modes. Additionally, pharmacokinetic properties were assessed through ADMET and SwissADME analyses, revealing improved profiles. Structure–activity relationship (SAR) analysis was also performed. Overall, these findings suggest that the synthesised compounds could serve as promising leads for the development of novel antimicrobial agents with enhanced biological efficacy for future pharmaceutical applications.

 

 

Author(s) Details

Sarkar M. A. Kawsar
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

S. M. Sajid Hasan Shammo
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Md. Farhan Labib
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Jahidul Islam Sajal
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Akibul Islam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Tasfia Tabassum
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Abonti Barua
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Niloy Bhattacharjee
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Md. Rithoan Hossain
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Nazia Islam
Laboratory of Carbohydrate and Nucleoside Chemistry (LCNC), Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong-4331, Bangladesh.

 

Please see the book here :- https://doi.org/10.9734/bpi/cbrp/v8/6586