Synthesis and antitumoral evaluation of indole alkaloid analogues containing an hexahydropyrrolo[1′,2′,3′:1,9a,9]imidazo[1,2-a]indole skeleton

The scope of acid-mediated cyclative additions of electrophiles to tryptophan-derived α-amino nitriles for the synthesis of 10b-substituted-1,2,4,5,10b,10c-hexahydropyrrolo[1′,2′,3′:1,9a,9]imidazo[1,2-a]indoles analogues of indole alkaloids has been studied. The results demonstrate the high potential of the methodology for the synthesis of 10b-bromo-derivatives, by bromination with NBS, 10b-allyl-derivatives, by bromo-allyl exchange, and 10b-prenyl-derivatives, by reaction with prenyl bromide in the presence of Mg(NO3)2·6H20. Some of the new pyrroloimidazoindole derivatives displayed moderate μM cytotoxicities in human cancer cell lines and at 10 μg/mL inhibited more than 50% EGFR or HIF-1α.

Figure optionsDownload as PowerPoint slide