Linked Life Data

9916012

Source:http://linkedlifedata.com/resource/pubmed/id/9916012

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-4-13
pubmed:abstractText
We have recently reported that tetrahedral metallocene complexes containing vanadium(IV) (vanadocene) have potent spermicidal activity against human sperm. The spermicidal activity was dependent on vanadium(IV) as the central metal ion within the bis-cyclopentadienyl (Cp2)-metal complex, but the variation of diacido groups and/or replacement with bidentate ligands coordinated to the Cp2-vanadium(IV) moiety also significantly modulated the spermicidal potency. To assess the structure-activity relationship between vanadocenes and other coordination complexes of vanadium(IV), a set of 11 oxovanadium(IV) complexes with different geometrical configurations were synthesized and evaluated for spermicidal activity by computer-assisted sperm analysis. These complexes included mono and bis ancillary ligands, 1,10-phenanthroline (phen): [VO(phen), VO(phen)2, VO(Me2-phen), VO(Me2-phen)2, VO(Cl-phen), and VO(Cl-phen)2]; 2,2'-bipyridyl (bipy): [VO(bipy), VO(bipy)2, VO(Me2-bipy), and VO(Me2-bipy)2], linked via nitrogen atoms; and 5'-bromo-2'-hydroxyacetophenone (acph): [VO(Br,OH-acph)2], linked via oxygen donor atoms. All 11 oxovanadium(IV) complexes elicited concentration-dependent spermicidal activity at micromolar concentrations (EC50 values: 5.5-118 microM). The bis-phenanthroline complex of oxovanadium(IV), VO(Cl-phen)2, was the most active, and the mono bipyridyl complex, VO(bipy), was the least active; the order of efficacy was VO(Cl-phen)2 > VO(phen)2 > VO(Br,OH-acph)2 > VO(Me2-phen) > VO(bipy)2 > VO(phen) > VO(Cl-phen) > VO(Me2-phen)2 > VO(Me2-bipy)2 > VO(Me2-bipy) > VO(bipy). The neutral complex, VO(Br, OH-acph)2, induced rapid sperm immobilization (T1/2 = 38 sec). The sperm-immobilizing activity of mono- and bis-ligated oxovanadium(IV) complexes was irreversible, since the treated sperm underwent apoptosis, as determined by the flow cytometric quantitation of mitochondrial membrane potential, surface Annexin V binding assay, and in situ DNA nick-end labeling of sperm nuclei. The percentages of apoptotic sperm quantitated by the flow cytometric assay correlated well with the spermicidal potency of oxovanadium(IV) complexes. These results provide unprecedented evidence that the spermicidal and apoptosis-inducing activities of vanadium(IV) complexes are determined by the oxidation state of vanadium as well as their geometry. Because of its rapid and potent sperm-immobilizing activity, the bromo-hydroxyacetophenone complex, [VO(Br,OH-acph)2], may be useful as a contraceptive agent.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-3363
pubmed:author
pubmed:issnType
Print
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
435-44
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Spermicidal activity of oxovanadium(IV) complexes of 1, 10-phenanthroline, 2,2'-bipyridyl, 5'-bromo-2'-hydroxyacetophenone and derivatives in humans.
pubmed:affiliation
Drug Discovery Program, Hughes Institute, St. Paul, Minnesota 55113, USA. odcruz@ih.org
pubmed:publicationType
Journal Article