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

Abstract

The scope of acid-mediated cyclative additions of electrophiles to tryptophan-derived α-amino nitriles for the synthesis of 10 b-substituted-1,2,4,5,10 b,10 c-hexahydropyrrolo[1′,2′,3′:1,9 a,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 10 b-bromo-derivatives, by bromination with NBS, 10 b-allyl-derivatives, by bromo-allyl exchange, and 10 b-prenyl-derivatives, by reaction with prenyl bromide in the presence of Mg(NO 3) 2·6H 20. 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.