Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

The Spermostatic and Microbicidal Actions of Quinones and Maleimides: Toward a Dual-Purpose Contraceptive Agent

Louise M. Hughes, Renate Griffith, Alison Carey, Trent Butler, Scott W. Donne, Ken W. Beagley and R. John Aitken
Molecular Pharmacology July 2009, 76 (1) 113-124; DOI: https://doi.org/10.1124/mol.108.053645
Louise M. Hughes
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renate Griffith
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alison Carey
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Trent Butler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott W. Donne
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken W. Beagley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. John Aitken
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

There is an urgent need to develop safe, effective, dual-purpose contraceptive agents that combine the prevention of pregnancy with protection against sexually transmitted diseases. Here we report the identification of a group of compounds that on contact with human spermatozoa induce a state of “spermostasis,” characterized by the extremely rapid inhibition of sperm movement without compromising cell viability. These spermostatic agents were more active and significantly less toxic than the reagent in current clinical use, nonoxynol 9, giving therapeutic indices (ratio of spermostatic to cytotoxic activity) that were orders of magnitude greater than this traditional spermicide. Although certain compounds could trigger reactive oxygen species generation by spermatozoa, this activity was not correlated with spermostasis. Rather, the latter was associated with alkylation of two major sperm tail proteins that were identified as A Kinase-Anchoring Proteins (AKAP3 and AKAP4) by mass spectrometry. As a consequence of disrupted AKAP function, the abilities of cAMP to drive protein kinase A-dependent activities in the sperm tail, such as the activation of SRC and the consequent stimulation of tyrosine phosphorylation, were suppressed. Furthermore, analysis of microbicidal activity using Chlamydia muridarum revealed powerful inhibitory effects at the same low micromolar doses that suppressed sperm movement. In this case, the microbicidal action was associated with alkylation of Major Outer Membrane Protein (MOMP), a major chlamydial membrane protein. Taken together, these results have identified for the first time a novel set of cellular targets and chemical principles capable of providing simultaneous defense against both fertility and the spread of sexually transmitted disease.

Footnotes

  • This work was supported by the Australian National Health and Medical Research Council [Grant 252441] and the Australian Research Council Centre of Excellence in Biotechnology and Development.

  • ABBREVIATIONS: STD, sexually transmitted disease; PKA, protein kinase A; AKAP, A kinase-anchoring protein; MOMP, major outer membrane protein; N9, nonoxynol 9; BWW, Biggers, Whitten and Whittingham medium; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; DHE, dihydroethidium; DTT, dithiothreitol; pCMBS, p-chloromercuribenzene sulfonic acid; Ptx, pentoxifylline; dbcAMP, dibutyryl cyclic adenosine monophosphate; PBS, phosphate-buffered saline; BSA, bovine serum albumin; MALDI-TOF, matrix-assisted-laser desorption-ionization-time-of-flight mass spectrometer; MBP, maltose binding protein; TI, therapeutic index; ROS, reactive oxygen species; Et, ethidium; 2OHEt, 2-hydroxyethidium; LUMO, lowest unoccupied molecular orbital; p-BQ, p-benzoquinone; BM, bismaleimide; p-NQ, p-naphthoquinone; RT, room temperature; PAGE, polyacrylamide gel electrophoresis; IFU, inclusion forming unit; SOD, superoxide dismutase.

  • ↵ Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

    • Accepted March 31, 2009.
    • Received November 22, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 76 (1)
Molecular Pharmacology
Vol. 76, Issue 1
1 Jul 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
The Spermostatic and Microbicidal Actions of Quinones and Maleimides: Toward a Dual-Purpose Contraceptive Agent
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

The Spermostatic and Microbicidal Actions of Quinones and Maleimides: Toward a Dual-Purpose Contraceptive Agent

Louise M. Hughes, Renate Griffith, Alison Carey, Trent Butler, Scott W. Donne, Ken W. Beagley and R. John Aitken
Molecular Pharmacology July 1, 2009, 76 (1) 113-124; DOI: https://doi.org/10.1124/mol.108.053645

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

The Spermostatic and Microbicidal Actions of Quinones and Maleimides: Toward a Dual-Purpose Contraceptive Agent

Louise M. Hughes, Renate Griffith, Alison Carey, Trent Butler, Scott W. Donne, Ken W. Beagley and R. John Aitken
Molecular Pharmacology July 1, 2009, 76 (1) 113-124; DOI: https://doi.org/10.1124/mol.108.053645
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of the selective action of paraherquamide A
  • Use-Dependent Relief of A-887826 Inhibition
  • Benzbromarone Relaxes Airway Smooth Muscle via BK Activation
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics