Herein we report a catalyst, metal and additive free generation of carbonyl ylides by blue LED irradiation of aryl diazoacetates in presence of aldehydes. The resulting ylides underwent [3+2] cycloaddition with substituted maleimides present in the reaction mixture to afford 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole in excellent yields. Fifty compounds were synthesized based on this scaffold. Molecular docking indicated them to be potential poly ADP ribose polymerase (PARP) inhibitor. Screening a representative member of the library against PARP-1 enzyme revealed a few potential inhibitors with IC50 of 600-700 nM. The phenotypic screening against MCF7, A549 and HepG2 cells furthermore indicated that these compounds selectively inhibit the proliferation of A549, HeLa and HepG2 cells with IC50 of 1-2 μM. The mechanism of action of the most active compound at the cellular level was investigated.
Keywords: Blue LED; Flow Chemistry; In-silico Studies; PARP-1 Inhibition; [3+2] Cycloaddition.
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