Reference

Mechanism for the stabilization in vivo of the aziridine precursor 2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride by serum proteins

Mechanism for the stabilization in vivo of the aziridine precursor 2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride by serum proteins. Louw, Ann; Swart, Pieter; De Kock, Schalk S.; Van Der Merwe, Kirsten J. (DEPARTMENT OF BIOCHEMISTRY, UNIVERSITY OF STELLENBOSCH, MATIELAND 7602, S. Afr.). Biochemical Pharmacology, 53(2), 189-197 (English) 1997 Elsevier. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Oral and i.p. administration of 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium chloride (Compd. A), an analog of Ph aziridine precursors that occur in the shrub Salsola tuberculatiformis Botsch., had a contraceptive effect on female Wistar rats with a concomitant decrease in total body, uterus, and ovary mass and an increase in adrenal mass. Compd. A elicited a Type II difference spectrum and inhibited the Type I deoxycorticosterone (DOC) induced difference spectrum of sheep adrenal cytochrome P450c11 in a manner similar to that of S2, a biol. active fraction isolated from S. tuberculatiformis. The effects of Compd. A on the spectral properties of P450c11 were diminished with time in PBS. Electrospray mass spectrometry (ES-MS) indicated that the rate of cyclization of Compd. A to the corresponding aziridine followed a time course similar to the attenuation of cytochrome P450c11 inhibition. It was concluded that the aziridine precursor, Compd. A, rather than aziridine itself, was the inhibiting agent of sheep adrenal P450c11. Addn. of sheep and rat plasma prevented the attenuation of the effect of Compd. A on the spectral properties of cytochrome P450c11. 5985-28-4 and 136529-71-0 which are cas registry numbers of substances are two of reagents here. Subsequent ES-MS anal. indicated that Compd. A was stabilized in plasma by sex hormone binding globulin and corticosteroid binding globulin. These results suggest a mechanism whereby natural plant products, which are highly reactive and unstable in vitro, can be stabilized by binding to plasma proteins, and so remain biol. active in vivo. .