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

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.