RESUMO
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 600-700â nM. The phenotypic screening against MCF7, A549 and HepG2â cells furthermore indicated that these compounds selectively inhibit the proliferation of A549, HeLa and HepG2â cells with IC50 of 1-2â µM. The mechanism of action of the most active compound at the cellular level was investigated.