Effect of the Chromone Core Substitution of Dirchromone on the Resultant Biological Activities

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2021-11, Vol.84 (11), p.2786-2794
• Main Authors: St-Gelais, Alexis, Alsarraf, Jérôme, Legault, Jean, Plourde, Joanne, Pichette, André
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antifungal Agents - pharmacology; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Chromones - chemical synthesis; Chromones - chemistry; Chromones - pharmacology; Humans; Structure-Activity Relationship
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.1c00385

Dirchromone is a bioactive vinyl sulfoxide-bearing chromone first isolated from the shrub Dirca palustris. Altogether, 32 of its derivatives were prepared to assess the effect of substitution of its chromone core upon activities against cancer cell lines, Gram-positive bacteria, and fungi (such as Candida albicans). All compounds were synthesized following a synthetic strategy involving Pummerer and soft-enolization Baker–Venkataraman rearrangements. Substituent position changes induced little variability on the activities tested. There was no correlation between cytotoxic and antibacterial effects, suggesting different underlying mechanisms of action. In particular, hydroxy group and cyanide substituents diminished cytotoxicity, with the latter featuring enhanced antibacterial activity. Higher homologues of 6-alkoxydirchromones also exhibited progressively emerging antifungal activity. Other modifications had moderate effects on cytotoxicity with some derivatives leading to increased potency. This behavior highlights the robustness of the natural dirchromone pharmacophore toward decoration, thus paving the way for more elaborate future drug design.