Antifertility and Antiproteolytic Activity of Activated N‐Carbobenzoxy Amino Acid Esters

Hall, Iris H.; Drew, J.H.; Sajadi, Z.; Loeffler, Larry J.

doi:10.1002/jps.2600680610

Cited by 20 publications

(3 citation statements)

References 18 publications

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“…During the last decade, several laboratories have attempted to develop acrosin inhibitors as vaginal contraceptives, using sterol sulfates (Burck and Zimmerman, 1980;Burck et al, 1982;Zimmerman et al, 1983), N-carbobenzoxy amino acid esters (Hall et al, 1979;Drew et al, 198l), and the aryl 4-guanidinobenzoates (Kaminski et al, 1986). At least in nonhuman species, the aryl 4-guanidinobenzoates are much more potent and less toxic than nonoxynol-9, encouraging their further development for clinical use.…”

Section: Discussionmentioning

confidence: 98%

Effect of Aryl 4-Guanidinobenzoates on the Acrosin Activity of Human Spermatozoa1

Kaminski

Smith

et al. 1987

Biology of Reproduction

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Certain aryl 4-guanidinobenzoates (AGs; inhibitors of proteinases, including the sperm enzyme acrosin) have been shown to be more potent vaginal contraceptives in rabbits and less toxic than nonoxynol-9, the active ingredient of most marketed vaginal contraceptive formulations. To determine if these AGs can contact sperm and inhibit acrosin when mixed with the entire human ejaculate for a short period of time (roughly imitating clinical conditions), the inhibitors were added to semen at various concentrations for 2 min, after which the seminal plasma and unbound inhibitor were removed from the sperm by Ficoll centrifugation. Subsequently, the total arginine amidolytic activity of the spermatozoa was determined spectrophotometrically after a combined treatment that resulted in extraction, proacrosin activation, and reaction with substrate. Dose-response curves were prepared. All AGs studied were effective inhibitors of the amidolytic activity under these conditions, with ED50 values (the dose levels at which half of the acrosin associated with 10(6) sperm is inhibited) ranging from 10(-5) to 10(-7) M. To determine the effect on the proteolytic activity of individual spermatozoa, the experiment was repeated with 4'-acetamidophenyl 4-guanidinobenzoate (AGB), and the protease released from the sperm was measured by the gelatin-plate assay. The inhibition results were similar to those obtained by extraction of the spermatozoa and measurement of amidolytic activity. Thus, when mixed with the human ejaculate, AGs interact rapidly with spermatozoa to inhibit both their arginine amidolytic and proteolytic activity (probably due primarily or only to inhibition of acrosin) and remain bound even after removal of the seminal plasma. These data encourage further study of the compounds for contraceptive purposes.

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Section: Discussionmentioning

confidence: 98%

Effect of Aryl 4-Guanidinobenzoates on the Acrosin Activity of Human Spermatozoa1

Kaminski

Smith

et al. 1987

Biology of Reproduction

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“…In addition, it has been reported that Cbz-Gly has antifertility effects, which can inhibit sperm acrosin or trypsin. 6 In practice, Cbz-Gly can also be used as an important organic intermediate in the industrial synthesis of pharmaceuticals, that is, delapril 7 and 6-deoxypenciclovir. 8 Solubility, as a significant characteristic of active pharmaceutical ingredients, is closely related to the bioavailability, crystal size distribution, and cocrystal formation.…”

Section: Introductionmentioning

confidence: 99%

“…As an amino-protective group, Cbz-Gly is commonly used for peptide synthesis − due to its stable physical properties and easy removal of Cbz. In addition, it has been reported that Cbz-Gly has antifertility effects, which can inhibit sperm acrosin or trypsin . In practice, Cbz-Gly can also be used as an important organic intermediate in the industrial synthesis of pharmaceuticals, that is, delapril and 6-deoxypenciclovir …”

Section: Introductionmentioning

confidence: 99%

Solubility Behavior of N-Carbobenzyloxyglycine in 14 Individual Solvents at Temperatures Ranging from 283.15 to 323.15 K

Huang

Qiu

et al. 2021

J. Chem. Eng. Data

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The solubility of N-carbobenzyloxyglycine (Cbz-Gly) in 14 neat solvents including alcohols (methanol, ethanol, ipropanol, n-propanol, n-butanol, i-butanol, and n-pentanol), ketones (acetone and 2-butanone), esters (methyl acetate and ethyl acetate), and other solvents (acetonitrile, dichloromethane, and water) was measured using the static gravimetric method at the temperature interval "T = 283.15−323.15 K" and the pressure "p = 98.8 kPa". The equilibrated solid phase of Cbz-Gly in the investigated solvent systems was characterized by the powder X-ray diffraction test. The rising temperature shows a positive effect on Cbz-Gly dissolution capacities in the monosolvents, and the following order is obtained: methanol > ethanol > i-propanol > npropanol > n-butanol > n-pentanol > i-butanol (alcohols) and acetone >2-butanone > methyl acetate > ethyl acetate > acetonitrile > dichloromethane > water (nonalcohols). The above solubility behavior is affected by the mutual constraints of polarity, hydrogen bonding, cohesive energy density, viscosity, and molecular structure. Additionally, two thermodynamic models (the modified Apelblat model and the Yaws model) were used to fit the measured solubility data.

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Carbobenzoxylglycine 1138‐80‐3

2004

Sax's Dangerous Properties of Industrial Materials

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Antifertility and Antiproteolytic Activity of Activated N‐Carbobenzoxy Amino Acid Esters

Cited by 20 publications

References 18 publications

Effect of Aryl 4-Guanidinobenzoates on the Acrosin Activity of Human Spermatozoa1

Effect of Aryl 4-Guanidinobenzoates on the Acrosin Activity of Human Spermatozoa1

Solubility Behavior of N-Carbobenzyloxyglycine in 14 Individual Solvents at Temperatures Ranging from 283.15 to 323.15 K

Carbobenzoxylglycine 1138‐80‐3

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