Design and chemical synthesis of selen–gemcitabine against multidrug-resistant Staphylococcus aureus

Abstract

Multidrug-resistant Staphylococcus aureus infection is a significant challenge to global health systems. We designed selen–gemcitabine to provide a dual inhibition mechanism and to reduce metabolic degradation by linking the amino group of gemcitabine with a selenoline ring, aiming to enhance antibacterial action. The synthetic routes were designed and optimized to adapt green chemistry using non-polluting reagents, such as cetyltrimethylammonium bromide and sodium hydroxymethylsulfonate to synthesize selenoline. In addition, the tetrabutylammonium fluoride process was optimized to selectively deprotect the tertiary butyldimethylsilyl group from gemcitabine’s 3′,5′-hydroxyl to gain high yield and purity. The half inhibitory concentration values of the synthesized selen–gemcitabine against several multidrug-resistant S. aureus ranged from 0.04 to 5.8 μM.