Synthesis and antibiotic potential of myxocoumarin-inspired chromene dione analogs

The rapid emergence of antibiotic resistance in recent years poses a substantial global health threat. Thus, the discovery of potent novel antibiotics is of utmost importance. One such compound class with promising antibiotic potential are the myxocoumarins from Stigmatella aurantiaca MYX-030, which exhibit exceptional antibiotic activities against several Gram-positive pathogens, including MRSA. Interestingly, the synthetic chromene dione precursors lacking the alkyl side chain also display promising antibiotic potential. Within this work, a focused library of chromene diones resembling the myxocoumarin A core structure was synthesized to explore structure-activity relationships. We were able to identify derivatives equipotent to the natural product but devoid of the alkyl chain and the nitro substituent to significantly facilitate synthetic access.