glycoside- and acyclic nucleoside-based 6-cyclohexyl-4-aryl-2-oxonicotinonitrile: synthesis and antimicrobial evaluation

Antimicrobial resistance is a global public health threat that signals the identification of new antimicrobial agents with different modes of action. the synthesis and the antimicrobial evaluations of a series of 2-oxonicotinonitriles (2-onns) derivatives are described. the parent 2-onn derivative 3 was synthesized by one-pot four-component reaction: acetyl cyclohexane, p-anisaldehyde, ethyl cyanoacetate, and nh4oac, in high yield. density functional theory geometrical equilibrium of the tautomeric forms of 3 concluded the predominance of the keto tautomer. base-catalyzed coupling of 3 with several organohalides/alkylating agents provided branching and solubilizing groups to the 2-onn derivative 3. alkylated onns and free acyclic nucleoside mimics/glycosides derived from the 2-onn derivative 3 were tested for their antibacterial and antifungal activities. the acyclic nucleoside mimic 13 and the n1-propargyl derivative 16 and n1-allyl derivative 18 showed significant activities against s. aureus, and m. luteus; meanwhile, significant anti-e. coli activity was observed with compounds 3 and 18. on the other hand, a significant antifungal activity was observed with 3 and with its n1-glucoside derivatives 4 and 5 against candida albicans and aspergillus niger.