1,12-substituted tetracyclines as antioxidant agents.
Novel hydroxypyrazoline derivatives of tetracycline and minocycline have been synthesized through the reaction of these tetracyclines with hydrazine. The formation of a new chiral center at C12 is stereospecific to give 12S-12-hydroxy-1,12-pyrazolinotetracycline. A reaction mechanism for the formation of these novel tetracycline derivatives has been proposed. Hydroxypyrazolinotetracyclines exhibit no binding to Mg2+ and Zn2+, features that are required for antibiotic activity and matrix metalloproteinase (MMP) inhibitions, respectively. The modification toward their hydroxypyrazolino derivatives significantly improved the antioxidant activities of tetracycline and minocycline, as shown by three commonly used assays (DPPH, ABTS+, and superoxide scavenging). 12S-Hydroxy-1,12-pyrazolinominocycline is a promising tetracycline-based antioxidant devoid of antibiotic properties and MMP inhibitory activity, which could be beneficial in the treatment of complications related to oxidative stress.
Lertvorachon
Jittiwud
J
National Research Council Canada, Biotechnology Research Institute, 6100 Royalmount Ave., Montréal, QC, Canada H4P 2R2.
Kim
Jong-Pyung
JP
Soldatov
Dmitriy V
DV
Boyd
Jason
J
Roman
Gheorghe
G
Cho
Sung Ju
SJ
Popek
Tomasz
T
Jung
Young-Sik
YS
Lau
Peter C K
PC
Konishi
Yasuo
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D003460:Crystallization; D004926:Escherichia coli / Q000187:drug effects; D006900:Hydroxylation; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013754:Tetracyclines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D011720:Pyrazoles; D013754:Tetracyclines; C031280:pyrazole; D015032:Zinc