title: Lack of antifertility properties of novel halogenated glycolytic inhibitors and the urinary excretion and metabolism of 1,6-dichloro-1,6-dideoxy-D-fructofuranose in the male rat.
abstract: The antifertility action of (R,S)-alpha-chlorohydrin administered orally to male rats was compared with that of several novel chlorinated compounds known to inhibit glycolysis and the kinematics of rat sperm in vitro. Oral gavage of 1,6-dichloro-1,6-dideoxy-D-fructofuranose (dichlorodideoxyfructose, DCF), 1-chloro-3-hydroxypropanone, its dimethylketal and bromopyruvate did not reduce the fertility of male rats below that of controls at the equivalent antifertility dose of (R,S)-alpha-chlorohydrin (5 mg/kg/day) or higher. As anticipated for a compound cleaved to products of (S)-chirality even high doses of DCF (200 mg/kg) showed no effect on renal function. 36Cl-Labelled DCF administered orally to male rats was eliminated only slowly in the urine (16% of the ingested dose excreted in 96 h). In the first 8 h, approximately 50% of DCF was excreted unchanged, 30% was excreted as 3-chlorolactate (BCLA), the oxidation product 3-chlorolactaldehyde and 25% as Cl-. By 24 h little DCF remained and the major metabolite (70%) was BCLA and 20% Cl-. The high rate of dechlorination is most likely responsible for the low antifertility action of DCF.
authors.affiliation: School of Molecular and Microbial Biosciences, Discipline of Biochemistry, University of Sydney, Sydney, NSW, Australia.
authors.forename: A R
authors.initials: AR
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Morin
authors.forename: W
authors.initials: W
authors.lastname: Bone
authors.forename: T G
authors.initials: TG
authors.lastname: Cooper
mesh_terms: D000096:Acetone / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D003837:Deoxy Sugars / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D005298:Fertility / Q000187:drug effects*; D005632:Fructose / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008745:Methylation; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000517:alpha-Chlorohydrin / Q000494:pharmacology
chemical_list: D003272:Contraceptive Agents, Male; D003837:Deoxy Sugars; D011773:Pyruvates; D000096:Acetone; D005632:Fructose; C059610:1,6-dichloro-1,6-dideoxyfructose; C017092:bromopyruvate; D000517:alpha-Chlorohydrin; C027160:1-hydroxy-3-chloroacetone