[The genetic activity of NO-containing agents is regulated by complex formation with intracellular iron].
This work is a part of a directional search for new crystal donors of nitric oxide (NO), which are promising for complex chemotherapy. The relationships between the physico-chemical properties of NO donors, their genotoxic and mutagenic activities, and the dependence on intracellular iron were studied. New crystal NO donors (di- and trinitrosyl iron complexes with synthetic ligands) were examined for the first time and compared with known NO donors containing natural ligands. All but one compound induced expression of the Escherichia coli sfiA gene belonging to the SOS regulon and exerted a mutagenic effect on Salmonella typhimurium TA1535. These effects were fully or significantly inhibited by the iron(II)-chelating agent o-phenanthrolin, depending on the mono- or binuclear structure of the ligands. The rate of donating free NO in solution did not positively correlate with the genotoxic activity of the crystal NO donors. The genetic activity of all NO donors proved to depend on intracellular iron.
Vasil'eva
S V
SV
Moshkovskaia
E Iu
EIu
Terekhov
A S
AS
Sanina
N A
NA
Aldoshin
S M
SM
D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics; D005296:Ferrous Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D009152:Mutagenicity Tests; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010618:Phenanthrolines / Q000494:pharmacology; D018085:Regulon; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
D029968:Escherichia coli Proteins; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D020030:Nitric Oxide Donors; D009942:Organometallic Compounds; D010618:Phenanthrolines; C053139:sulA protein, E coli; D009569:Nitric Oxide; D007501:Iron; C025205:1,10-phenanthroline