title: In vitro activity of artemisone and artemisinin derivatives against extracellular and intracellular Helicobacter pylori.
abstract: The in vitro activity of the new artemisinin derivative artemisone as well as other molecules of the same class against Helicobacter pylori and their effects when combined with standard antibiotics were evaluated. Since H. pylori can be internalised into gastric epithelial cells, the effects of artemisinin, dihydroartemisinin and artemisone against intracellular H. pylori were also investigated. Bacteriostatic [minimum inhibitory concentration (MIC)] and bactericidal [minimum bactericidal concentration (MBC)] activities were assessed against 24 clinical strains of H. pylori with different antibiotics susceptibilities. Artemisone showed MIC50 and MIC90 values of 0.25 mg/L and 0.5 mg/L, respectively, and an MBC50 value of 0.5 mg/L. Artemisone was synergistic with amoxicillin in 60% of strains, with clarithromycin in 40% and with metronidazole in 20%. There was no interaction between artemisone and omeprazole or bismuth citrate. Against intracellular H. pylori, only dihydroartemisinin at 2× MIC caused a 1 log10 CFU decrease after 18 h and 24 h of incubation. This is the first demonstration in vitro of the activity of artemisinin derivatives against intracellular H. pylori and indicates that artemisone has the potential to be efficacious for the treatment of H. pylori infection, especially in combination with antibiotics.
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy. Electronic address: francesca.sisto@unimi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sisto
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Maria Maddalena
authors.initials: MM
authors.lastname: Scaltrito
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Masia
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bonomi
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Coccè
authors.affiliation: Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marano
authors.affiliation: Centre of Excellence for Pharmaceutical Sciences, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Haynes
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Miani
authors.affiliation: Dipartimento di Scienze Biomediche, Chirurgiche ed Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milan, Italy.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Farronato
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Taramelli
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D004357:Drug Synergism; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; C514498:artemisone; C031327:artemisinin
keywords: Artemisinin; Drug resistance; Gastric cell invasion; Helicobacter pylori