Synthesis and antimicrobial activity of geranyloxy- and farnesyloxy-acetophenone derivatives against oral pathogens.
The compounds 2',6'-dihydroxy-4'-geranyloxyacetophenone (1) and 2',6'-dihydroxy-4'-farnesyloxy-acetophenone (2) are oxyprenylated secondary metabolites extracted from plants belonging to the Rutaceae family. In this study, 1 and 2 were synthesized and tested for their antimicrobial activity toward major oral pathogens. Compounds 1 and 2 were synthesized by selective prenylation of 2,4,6-trihydroxyacetophenone at the 4' position with geranyl and farnesyl bromide, respectively. Compound 1 showed stronger antimicrobial activity than 2 against major oral pathogens, including Gram positive bacteria (Streptococcus mutans, Streptococcus sobrinus), Gram negative bacteria (Prevotella intermedia, Porphyromonas gingivalis) and Candida albicans. Evidences were obtained that the mode of action of 1 and 2 may be related to their iron-chelating property. This study suggests that 1 and 2 may represent potential natural molecules for the prevention/treatment of common oral infections, including dental caries, periodontal disease, and candidiasis.
Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, Québec City, QC, Canada.
Laetitia
L
Bonifait
Annie
A
Marquis
Salvatore
S
Genovese
Francesco
F
Epifano
Daniel
D
Grenier
D000098:Acetophenones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002177:Candidiasis / Q000188:drug therapy; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D003731:Dental Caries / Q000188:drug therapy; D007501:Iron / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000382:microbiology*; D010510:Periodontal Diseases / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017861:Porphyromonas / Q000187:drug effects; D054876:Prenylation; D018720:Prevotella / Q000187:drug effects; D027821:Rutaceae / Q000737:chemistry*; D013291:Streptococcus / Q000187:drug effects
C576421:2',6'-dihydroxy-4'-farnesyloxy-acetophenone; C576420:2',6'-dihydroxy-4'-geranyloxyacetophenone; D000098:Acetophenones; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002614:Chelating Agents; D010936:Plant Extracts; C107067:2,4,6-trihydroxyacetophenone; D007501:Iron