14 Feb

Aryl Phosphate Derivatives of Bromo-Methoxy-Azidothymidine: RESULTS(6)


Spermicidal Activity of AZT Derivatives Was Irreversible

In order to determine whether the SIA of WHI-05 or WHI-07 was reversible, sperm exposed to 100 ^M of either compound for 30 min were washed and resuspended in fresh sperm motility assay medium, and sperm motility was reassessed by CASA (Table 1). No recovery in sperm motility was observed, indicating that the drug-induced sperm immobilization was irreversible. Direct addition of compounds WHI-05 and WHI-07 to semen diluted in PBS resulted in complete loss of motility as assessed by CASA (data not shown). Thus, the spermicidal activity was not affected by seminal plasma. buy ventolin inhalers

Lack of Membrane Disruption by Spermicidal AZT Derivatives

Because the great majority of spermicidal compounds are believed to immobilize sperm as a result of a detergent-type action on the sperm plasma membrane, we also tested the effects of WHI-05 and WHI-07 on sperm plasma membrane permeability by flow cytometric analysis of PI-stained sperm and acrosome integrity by examination of FITC-lectin-, TOTO-3 iodide-, and Nile red-stained sperm using confocal laser scanning microscopy. Despite complete immobilization of sperm in the presence of WHI-05 and WHI-07, < 3% of sperm were permeable to PI after 4 h of incubation with these compounds. In acrosome integrity studies, WHI-05- and WHI-07-treated sperm (similar to sham-treated sperm) remained acrosome intact (97 ± 2% and 93 ± 5.6%, respectively) after 3 h of incubation at a concentration of 100 ^M despite a complete loss of motility.

TABLE 1. Effect of brief exposure and sperm washing on spermicidal activity of aryl phosphate derivatives of bromo-methoxy-AZT.

Treatment (30 min) % Motilitya
Prewash Postwash
DMSO (0.1%) 86 ± 3 91 ± 4b
WHI-05 (100 ^M) 17 ± 4 0
WHI-07 (100 ^M) 0 0

a Sperm motility was assessed by CASA.
b CASA was performed after 30 min of incubation in BWW-0.3% BSA medium without DMSO or drugs.

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