Antibacterial activities of new synthetic divalent cation chelators.
A series of new synthetic ligand compounds which chelate divalent cations was examined for the antibacterial activities of the compounds. Only 2 of 14 synthetic chelators, 9-trans-anthryl-1, 4, 8, 11-tetraaza-tetradecane (No. 6) and bis(2-pyridyl)methylamine (No. 13) showed antibacterial activities, whereas none of the diamines, hydrophilic triamines nor tetramines showed antibacterial activities. Chelators No. 6 and No. 13 inhibited the growth of both Gram-negative and -positive bacteria at doses of 25-200 microg/ml, comparable to those of common antibiotics such as polymixin B, fosfomycin and macrolides. Ethylenediaminetetraacetate (EDTA) potentiated these antibacterial activities, whereas an inhibitory effect of Mg2+ on the MICs of these chelators was observed. Moreover, these chelators enhanced the leakage of periplasmic beta-lactamase. It is therefore suggested that chelators No. 6 and No. 13 disrupt both the membranes and cytoplasmic functions of bacteria, resulting in cell death.
Ashoori
M
M
Department of Oral Surgery, Nagoya University School of Medicine, Aichi, Japan.
Ohta
M
M
Ohsuka
S
S
Shibayama
K
K
Horii
T
T
Ueda
M
M
Kurosaki
H
H
D000873:Anthracenes / Q000138:chemical synthesis / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D002413:Cations, Divalent; D002614:Chelating Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development; D008024:Ligands; D008744:Methylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D012475:Salmonella / Q000187:drug effects* / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development
C121053:9-anthryl-1,4,8,11-tetraazatetradecane; D000873:Anthracenes; D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D002413:Cations, Divalent; D002614:Chelating Agents; D008024:Ligands; D008744:Methylamines; D011725:Pyridines; C121054:bis(2-pyridyl)methylamine