A potential anti-implantation and spermicidal strategy: putative derivatives of nonoxynol-9 and anti-inflammatory agents and their spermicidal activity.
OBJECTIVE
We report the synthesis of novel ester derivatives of nonoxynol-9, an approved spermicidal agent, using the non-steroidal inflammatory drugs (NSAIDs) ibuprofen and indomethacin. Indomethacin has previously been shown to inhibit the implantation of the fertilised ovum into the uterus wall of pregnant rats. It is proposed that nonoxynol-9, in combination with a non-selective NSAID may exhibit both anti-implantation and spermicidal properties.


METHODS
Both novel derivatives and nonoxynol-9 were then tested on boar spermatozoa in order to establish if spermicidal activity was retained following the esterification.


RESULTS
The results showed that both the ibuprofen and indomethacin derivatives enabled complete cell death of boar spermatozoa at a concentration of 100 microg ml(-1), which is comparable to nonoxynol-9 at the same concentration.


CONCLUSIONS
These results indicate that NSAID derivatives of nonoxynol-9 retain the activity of the parent molecule and may have other advantages associated with the molecular incorporation of the NSAID moieties and their anti-implantation activity.
Ingram
Matthew J
MJ
School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Moulsecoomb, Brighton BN2 4GJ, UK. mji@bton.ac.uk
Zeller
Edel
E
Moss
Gary P
GP
Hall
Charlotte E
CE
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017137:Nonoxynol / Q000008:administration & dosage / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects*; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D013089:Spermatocidal Agents; D017137:Nonoxynol; D007052:Ibuprofen; D007213:Indomethacin