Small molecular inhibitors of miR-1 identified from photocycloadducts of acetylenes with 2-methoxy-1,4-naphthalenequinone.

Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure-activity relationship of the miR-1 inhibitor.