Synthesis of <i>N</i>‑Substituted Acenaphtho[1,2‑<i>b</i>]pyrroles and Dibenzo[<i>e,g</i>]indoles with Promising Antileukemic Activity from Morita-Baylis-Hillman Adducts.

Abstract

This study investigates a novel synthetic pathway for <i>N</i>-substituted polycyclic heterocycles with potential antileukemic activity. The strategy employs Morita-Baylis-Hillman (MBH) adducts derived from polycyclic 1,2-diketones such as acenaphthoquinone and phenanthrene-9,10-dione. The key steps involve acetylation of the MBH adducts followed by cyclization with primary amines to afford <i>N</i>-heterocycles, specifically acenaphtho-[1,2-<i>b</i>]-pyrroles and dibenzo-[<i>e,g</i>]-indoles. The synthesized compounds were evaluated in vitro against leukemia cell lines (Jurkat and NB4). Several derivatives exhibited promising activity, with compound 4b showing particularly strong potency against the NB4 cell line. Overall, this work advances the development of novel antileukemic agents and underscores the potential of <i>N</i>-substituted polycyclic heterocycles in leukemia therapy.