Synthesis and Biological Activities Assessment of 4-, 6-, and 9-Phenylphenalenone Derivatives

By means of a facile method, sixty analogs of 4-, 6-, and 9-phenylphenalenone were synthesized, of which forty-nine compounds are novel. These synthesized compounds were first evaluated for their biological activities against phytopathogenic fungi (Alternaria solani, Cercospora arachidicola, Fusarium omysporum, Gibberella zeae, and Physalospora piricola), tobacco mosaic virus (TMV), as well as human cancer cells (p53-wild-type HCT-116 colon cancer cells, p53-mutated HT-29 colon cancer cells, PANC-1 pancreatic cancer cells, and PC-3 prostate cancer cells) systematically. 9 o was sufficiently effective against all the tested phytofungal strains and is worth further structural optimization for developing into a more potent fungicidal agent. Some effects of 6 o and 9 d (inactivation, curing, or protection) against TMV infection were more efficient than the commercial antiviral agents ribavirin and ningnanmycin. These could be selected as potential antiviral lead compounds. With regards to cytotoxicity, the cytotoxic compounds 6 p (IC₅₀ 1.6 μM in HCT-116 cells) and 9 c (IC₅₀ 2.6 μM in PC-3 cells) are worth further structural modification to achieve a higher antitumor potency.