Skip Navigation


Hum. Reprod. Advance Access first published online on June 2, 2005
This version published online on June 23, 2005
Human Reproduction, doi:10.1093/humrep/dei041
This Article
Right arrow FREE Full Text (PDF ) Freely available
Right arrow All Versions of this Article:
20/8/2301    most recent
dei041v2
dei041v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Gupta, G.
Right arrow Articles by Batra, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gupta, G.
Right arrow Articles by Batra, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received November 4, 2004
Revised March 22, 2005
Accepted March 31, 2005

Article

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

G. Gupta 1*, R.K. Jain 1, J.P. Maikhuri 1, P.K. Shukla 2, M. Kumar 2, A.K. Roy 3, A. Patra 3, V. Singh 3, and S. Batra 3

1 Divisions of Endocrinology, Central Drug Research Institute, Lucknow 226 001, India
2 Fermentation Technology, Central Drug Research Institute, Lucknow 226 001, India
3 Medicinal Chemistry, Central Drug Research Institute, Lucknow 226 001, India

* To whom correspondence should be addressed.
G. Gupta, E-mail: gupta.gopal{at}rediffmail.com


  Abstract

BACKGROUND: The continued endeavour to design novel, non-detergent molecules that can be useful as topical, prophylactic contraceptives has led to the discovery of substituted isoxazolecarbaldehydes as a new class of compounds exhibiting both spermicidal and acrosin inhibitory activities simultaneously. METHODS: Normal human semen samples were used to detect the spermicidal and acrosin inhibitory activities of the new compounds. Lactobacillus, HeLa and Candida cultures were used to determine the safety of compounds towards normal vaginal flora, their cytotoxicity and anti-fungal activity. Supravital staining and the hypo-osmotic swelling test (HOST) were used to detect the effect on sperm membrane integrity. Nonoxynol-9 (N-9) was used as a reference standard. RESULTS: The 5- and 3-substituted isoxazolecarbaldehydes showed significant spermicidal [minimum effective concentration (MEC)=0.005-2.5%] and acrosin inhibitory (IC50=3.9-58 x 10-4 mol/l) activities in several molecules along with weak fungicidal activity against Candida albicans. Lineweaver-Burk and Dixon plot analysis of a representative structure showed non-competitive inhibition of human acrosin enzyme, and the most potent acrosin inhibitors also considerably diminished the induction of the acrosome reaction by Ca2+ ionophore. Some compounds were found to be significantly safer than N-9 towards Lactobacillus acidophilus in vitro at their respective spermicidal MECs. In the cytotoxicity assay, the IC50 of these compounds towards the HeLa cell line was of the same order as N-9 (0.9-0.1 mmol/l); however, in contrast, the compounds exhibited only a moderate effect on sperm membrane integrity. CONCLUSIONS: This study indicates that 5- and 3-substituted isoxazolecarbaldehydes are ‘first generation’ multifunctional, spermicidal molecules that hold promise for development as topical contraceptives with useful associated activities that can add considerably to their effectiveness, safety and prophylaxis.

Keywords: acrosin inhibition; anti-fungal; isoxazolecarbaldehydes; spermicide; topical microbicide.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum ReprodHome page
R. K. Jain, A. Jain, J. P. Maikhuri, V. L. Sharma, A. K. Dwivedi, S.T.V.S. Kiran Kumar, K. Mitra, V. K. Bajpai, and G. Gupta
In vitro testing of rationally designed spermicides for selectively targeting human sperm in vagina to ensure safe contraception
Hum. Reprod., March 1, 2009; 24(3): 590 - 601.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R.K. Jain, J.P. Maikhuri, S.T.V.S. Kiran Kumar, V.L. Sharma, A.K. Dwivedi, K. Mitra, V.K. Bajpai, and G. Gupta
Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro
Hum. Reprod., March 1, 2007; 22(3): 708 - 716.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.