Precursor‐Directed Synthesis of Apoptosis‐Initiating N‐Hydroxyalkyl Phenylbenzoisoquinolindione Alkaloids

Abstract

Abstract A precursor‐directed approach to access N‐hydroxyalkyl phenylbenzoisoquinolindiones (PBIQs) has been developed. Incubation of plant material of Xiphidium caeruleum with hydroxylamines of various chain lengths (C2, C4, C6, C8, C10 and C12) resulted in 11 new 5‐hydroxy‐ and 5‐methoxy PBIQs with different N‐hydroxyalkyl side chain lengths. The antiproliferative effect and the cytotoxicity against HUVEC, K‐562, and HeLa cell lines of 26 previously reported PBIQs and the 11 newly synthesized N‐hydroxyalkyl PBIQs was determined for the first time. The results revealed that introducing long‐chain N‐aliphatic amine moieties improved the antiproliferative effect and cytotoxicity of PBIQs when compared to derivatives with N‐amino acids as side chains.

Keywords

• antiproliferative effect
• apoptosis
• cytotoxicity
• phenylbenzoisoquinolindione
• precursor-directed synthesis