Synthesis of 2-(Quinoxalin-2-yl)acetamides and Their Preliminary Cytotoxic and Antibacterial Activity.

Quinoxaline is an aza-heterocycle found in some bioactive compounds. Thus, to enhance the pharmacological scope of this nucleus, we report a series of 19 acetamides decorated with a quinoxaline core. The synthesis involved the linkage of previously constructed bromoacetamides and hydroxyphenyl quinoxalines via an SN2 reaction. The first series considered a 1,4-substituted phenyl ring as a linker, and some derivatives showed moderate antibacterial activity against a panel of ESKAPE pathogens, especially against methicillin-resistant Staphylococcus aureus (inhibition ranging from 10% to 60% at 100 µM). Interestingly, the activity dropped in the 1,3- and 1,2-regioisomers. Furthermore, we tested the series against relevant human cancer cell lines, in which the ethyl derivative 10c inhibited the growth of breast, prostate, and colon tumors (43%, 48%, and 66%, respectively), whereas COS-7 cells showed only 7.8% inhibition. Although these are preliminary in vitro findings, we corroborate the applicability of the quinoxaline heterocycle in the design of potential candidates against relevant pathologies.