Synthesis of Azaphenalenone Derivatives Using Aldrone Condensation and Evaluation of Their Anticancer Activities

Abstract

ABSTRACT Phenalenones (PNs), popular as antifungal, antimicrobial, and anticancer agents, are a fascinating class of naturally occurring photosensitizers. In spite of their importance, doping of the main core of PNs remains unexplored. Herein, we report a facile and green approach to prepare N‐doped PNs or aza phenalenones (APNs) for the first time. We accomplished the goal by trapping unstable peri ‐naphthoisatogen, prepared using a modified aldrone condensation reaction. Different types of primary amines were used as nucleophile to synthesize seven APNs. Structures of the APNs were unambiguously characterized using NMR spectroscopy, mass spectrometry, and x‐ray crystallography. Anticancer activities of the APNs were evaluated against oral cancer cells. Among them, the APN derivative of 3‐aminopyridine demonstrated the most potent anticancer activity with high selectivity against oral cancer cells. We further investigated the mechanism underlying the anticancer activity of this lead compound.