Synthesis, Antibacterial and Cytotoxicity Assessment of Modified Uridine Molecules

Abstract

Nucleoside derivatives continue to play an essential role in the treatment of various diseases, thus the consideration of the importance of nucleoside analogues, we have synthesized a series of nucleoside molecules i.e., uridine derivatives. The reaction to uridine molecules with N-acetylsulfanilyl chloride by the direct acylation yielded corresponding 5´-O-N-acetylsulfanilyluridine having ribose sugar moiety. To obtain newer products, the 5´-O-N-acetylsulfanilyluridine derivative was further transformed into a series of 2´,3´-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The purity and structure of the obtained products have been confirmed by thin-layer chromatography, IR, ¹H-NMR spectroscopy, physicochemical and elemental analysis. All the synthesized uridine derivatives were screened for their in vitro antibacterial activity against six human pathogenic bacterial strains. The study revealed that the selectively acylated derivatives 5´-O-N-acetylsulfanilyl-2´,3´-di-O-lauroyluridine (7) and 5´-O-N-acetylsulfanilyl-2´,3´-di-O-pivaloyluridine (10) showed the highest inhibition against Staphylococcus aureus and Bacillus cereus, respectively. Another noteworthy observation was that the uridine derivatives were found comparatively more effective against Gram-positive bacteria than that of Gram-negative bacteria. Besides, the test compounds were also tested for cytotoxicity by brine shrimp lethality bioassay and compounds showed different rate of mortality with different concentrations. Hence, these synthesized derivatives might be used as antibacterial agents and are promising drug candidates for future therapeutic uses.