Platanic acid derived amides are more cytotoxic than their corresponding oximes

Abstract

Albeit platanic acid has been known since 1956, its potential to act as a valuable starting material for the synthesis of cytotoxic agents has been neglected for many years. Hereby we describe the synthesis of a small library of amides and oximes derived from 3-O-acetyl-platanic acid, and the results of their screening as cytotoxic agents for several human tumor cell lines. As a result, while the cytotoxicity of the oximes was diminished as compared to the parent amides, the homopiperazinyl amide 5 held the highest cytoxicity (EC50 = 0.9 μM for A375 human melanoma cells). Extra FACS and cell cycle measurements showed compound 5 to act onto A375 cells rather by apoptosis than by necrosis.