Molecular Human Reproduction, Vol 4, 683-693, Copyright © 1998 by Oxford University Press
OJ Di Cruz, P Ghosh and FM Uckun
Transition metal complexes containing vanadium IV have been shown to
modulate the cellular redox potential and catalyse the generation of
reactive oxygen intermediates (ROI). Since sperm function is exquisitely
susceptible to ROI, we examined the effects of stable chelate complexes of
vanadocenes on human sperm motility. We synthesized seven structurally
distinct chelate complexes of bis(cyclopentadienyl)vanadium(IV) with
bidentate ligands [i.e. vanadocene acetylacetonato monotriflate (VDacac),
vanadocene hexafluoro acetylacetonato monotriflate (VDHfacac), vanadocene
N-phenyl benzohydroxamato monotriflate (VDPH), vanadocene acethydroxamato
monotriflate (VDH), vanadocene catecholate (VDCAT), vanadocene bipyridino
ditriflate (VDBPY), and vanadocene dithiocarbamate monotriflate (VDDTC)],
and evaluated their spermicidal activity using computer-assisted sperm
analysis (CASA; Hamilton-Thorne). All seven chelate complexes of vanadocene
elicited potent spermicidal activity at micromolar concentrations (EC50
values: 3.9-106 microM) without affecting the sperm acrosome integrity. The
catecholate and acetylacetonate complexes of vanadocene were the most
active and the bipyridyl complex the least active with an order of efficacy
VDCAT > VDacac > VDDTC > VDPH > VDH > VDHfacac > VDBPY.
The spermicidal activity of chelate complexes of vanadocenes was rapid and
irreversible since the treated spermatozoa underwent apoptosis, as
determined by the flow cytometric analysis of mitochondrial membrane
potential, surface annexin V binding assay, in-situ nick-end labelling of
sperm nuclei, and confocal laser scanning microscopy. These results provide
unprecedented evidence that chelate complexes of vanadocene with bidentate
ligands have spermicidal and apoptosis inducing properties. These
vanadocene complexes, especially VDacac, may be useful as contraceptive
agents.
JOURNAL ARTICLE
Spermicidal activity of chelated complexes of bis(cyclopentadienyl)vanadium(IV)
Drug Discovery Program, Hughes Institute, St Paul, Minnesota 55113, USA.
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