Oral Antifertility Effects of Halo Propanediol Derivatives in Male Rats

Abstract

Ten derivatives of halo propanediol were tested orally for male antifertility effects in adult Sprague-Dawley rats. Six of these compounds were effective in inducing temporary sterility at a daily dose ranging from 2\m=.\5to 5 mg/rat. When administered over a minimum period of 7 days, these minimum effective doses did not interfere with the mating behaviour and spermatogenesis even during prolonged medication. However, at ten times the minimum effective dose, Compounds III (1-chloro-2,3-propanediol) and VII (1-chloro-2,3-bis[tetrahydropyran-2-yloxy]propane) caused severe testicular damage and irreversible sterility, while Compound X (4-[chloromethyl]-2-pentyl-1,3-dioxolane) did not. Our studies confirm that the presence of an \g=a\-chlorohydrin group is essential in halo propanediol derivatives for antifertility effects in male rats.

Effect of 4-Chloromethyl-2-Methyl-2-Pentyl-1,3-Dioxolane (Ay-22,352) on the Fertilizing Ability of Hamster Epididymal Spermatozoa

“…In the rat, AY-22,352 was found to be a more effective chemosterilant than achlorohydrin (Banik et al, 1972). The present results compared with the antifertility effects of -chlorohydrin in the hamster (Lubicz-Nawrocki & Chang, 1974a, b) show that this analogue of -chlorohydrin is almost twice as effective in inducing sterility.…”

Glycerol 3-phosphate dehydrogenase of boar spermatozoa: inhibition by -bromohydrin phosphate

“…Attempts to study the action of (R,S)-a-chlorohydrin-l-phosphate on the metabolism of glycerol 3-phosphate were hindered by the presence of wide-range phosphatase activity in the samples of boar spermatozoa being used which converted (S)-achlorohydrin-1-phosphate to (S)-a-chlorohydrin, thereby allowing the formation of (S)-3-chlorolactaldehyde . To overcome this, we have synthesized (R,S)-abromohydrin-1-phosphate and confirmed that this compound also inhibited the metabolism of glycerol 3-phosphate without affecting that of any other substrate since its hydrolysis, to (R,S)-a-bromohydrin, produces a compound that has no action on spermatozoa either in vivo (Banik et al, 1972) or in vitro . The use of 3-chloro-lhydroxypropanone (Jones el al, 1986) and 3-bromopyruvate (Stevenson and Jones, 1985) at 34°C The sealed flasks were transported to the laboratory where the spermatozoa were flushed from the epididymides with PBS (34°C) from incisions made in the third and fourth segments of the cauda according to the classification of Holtz and Smidt (1976).…”

Antifertility Activity and Toxicity of a-Chlorohydrin Aromatic Ketal Analogues in Male Rats

“…J ones and O'Brien (1980) studied the metabolism by the rat of two ketal derivatives which had been shown previously to have antifertility activities in the rat comparable to that of a-chlorohydrin (Banik et al 1972;Hirsch et al 1975). Both compounds produce iJ-chlorolactate, the major oxidative metabolite of a-chlorohydrin, indicating that these ketal derivatives are degraded to a-chlorohydrin.…”