Synthesis and biological activities of some new antimicrobial and cytotoxic 5-/7-/8-phenylphenalenone derivatives

Utilizing a facile method, sixty-three analogs of the 5-/7-/8-phenylphenalenone core were synthesized, of which sixty compounds are new. These compounds were systematically evaluated for their biological activities against phytopathogenic fungi (Alternaria solani, Cercospora arachidicola, Fusarium oxysporum, Gibberella zeae and Physalospora piricola), the tobacco mosaic virus (TMV), as well as human cancer cell lines (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). 5p and 8m showed a broader fungicidal spectrum of activity among all of the target compounds and are worthy of further structural optimization to develop more potent fungicidal agents. Some of the effects of 7c and 8m (inactivation, curing, or protection) against TMV infection were more efficient than the commercial antiviral agents' ribavirin and ningnanmycin. These analogs could be selected as potential antiviral hit compounds. Cytotoxic compound 7c (IC₅₀ 1.8 μM in HT-29 cells) is worth pursuing for further structural modification to achieve a higher antitumor potency. © 2023 Phytochemical Society of Europe