title: In vitro antibacterial activity of different adenosine analogues.
abstract: Nucleoside analogues may represent good candidates for the discovery of new antibacterial agents, therefore, a library of adenosine analogues was assessed for their antibacterial activity, and the relationship between the structure and activity of these molecules was outlined. Antibacterial activity was evaluated against that of reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Escherichia coli and Pseudomonas aeruginosa. We tested 54 adenosine analogues, modified both at ribose and base moieties, including adenine and 1/3-deazaadenine derivatives substituted in the 2- and/or N(6)-positions and bearing N-9 sugar moieties, such as ribose, 2'-deoxyribose, 3'-deoxyribose, 2',3'-dideoxyribose or cycloalkyl groups like cyclopentane. The data obtained, MIC and minimal bactericidal concentrations demonstrated that the presence of bulky substituents such as cycloheptyl and cyclooctyl rings on the N(6)-amino, together with a chlorine atom in the 2-position, conferred antibacterial activity against the Gram-positive group with MIC values ranging from 16 to 128 mg l(-1). The intact sugar moiety seemed to be not essential for antimicrobial activity and nucleosides bearing deoxyribose or cyclopentyl groups associated with bulky substituents in N(6)-position showed good antimicrobial properties. Furthermore, N-1 proved to be non-crucial and the 2-chloro-N(6)-cyclooctyl-1-deaza-3'-deoxyadenosine and 2',3'-dideoxyadenosine compounds were among the more active in the series with an MIC of 32 mg l(-1) against Staph. aureus and Strep. pneumoniae. None of the analogues was active against the two gram-negative species tested. Hence, adenosine derivatives bearing bulky substituents in the N(6)-position may represent good lead compounds for the future discovery of a novel series of antibacterial agents.
authors.affiliation: School of Pharmacy, Microbiology Unit, University of Camerino, via Gentile III da Varano, 62032 Camerino (MC), Italy.
authors.forename: Luca A
authors.initials: LA
authors.lastname: Vitali
authors.affiliation: School of Biosciences and Biotechnology, University of Camerino, via Gentile III da Varano, 62032 Camerino (MC), Italy.
authors.forename: Dezemona
authors.initials: D
authors.lastname: Petrelli
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy.
authors.forename: Catia
authors.initials: C
authors.lastname: Lambertucci
authors.affiliation: School of Biosciences and Biotechnology, University of Camerino, via Gentile III da Varano, 62032 Camerino (MC), Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Prenna
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Volpini
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032 Camerino (MC), Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Cristalli
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000241:Adenosine; D004121:Dimethyl Sulfoxide