Acrosin inhibitor, 4'-acetamidophenyl 4-guanidinobenzoate, an experimental vaginal contraceptive with anti-HIV activity.
Serine proteases are involved in a wide variety of seemingly unrelated physiological functions including capacitation of the spermatozoa and potentiation of human immunodeficiency virus (HIV) infection. The experimental vaginal contraceptives derived from 4-guanidinobenzoic acid act through inhibition of acrosin--a serine protease from the sperm. The serial ten-fold dilutions of 4'-acetamidophenyl 4-guanidinobenzoate (AGB) were tested in vitro for the effect against HIV infection by assaying the suppression of de novo p24 synthesis in virus-inoculated MT-4 T lymphocytes. The results reveal that complete inhibition of HIV occurred at 100 micrograms/ml--a dose corresponding to previously reported concentrations responsible for preventing fertilization in rabbits. These findings suggest that serine protease inhibitors and in particular the guanidinobenzoates, reported to be up to 100-fold more potent and less irritating than nonoxynol-9, can be potentially operative against sexual transmission of HIV.
Bourinbaiar
A S
AS
Department of Biochemistry, New York University Medical Center, NY 10016, USA.
Lee-Huang
S
S
D000176:Acrosin / Q000037:antagonists & inhibitors*; D000998:Antiviral Agents / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects*; D006801:Humans; D013089:Spermatocidal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014621:Vagina
D000998:Antiviral Agents; D001565:Benzoates; D006146:Guanidines; D013089:Spermatocidal Agents; C058095:4'-acetamidophenyl 4-guanidinobenzoate; D000176:Acrosin