The influence of biologically active compounds from Salsola tuberculatiformis Botsch. on steroid protein interactions

Allie, Fatima (1998)

Thesis (M. Sc.) -- University of Stellenbosch, 1998.

Thesis

ENGLISH ABSTRACT: This study forms part of an ongoing investigation into the syndrome of prolonged gestation in sheep and contraception in rats, caused by Namibian shrub, Salsola tuberculatiformis Botsch. Evidence was obtained from studies with A. tuberculatiformis extracts, that compounds in the shrub pertrubed adrenal steroidogenesis in the rat and interfered with the binding of the natural subtrate, deoxicortocosterone, to sheep adrenal cytochrome P450c11. Swart described the isolation o fone of the active compounds from the shrub, named S2. The S2 fraction was found to consist of a mixture of an extremely labile compound plus one or more stable components, one of which is synephrine. In an aqueous medium synephrine is a breakdown product of the S2 fraction. Derivitization studies suggested that the active component in S2 was a labile hydroxyphenyl-aziridine or the corresponding open chain precursor. A more stable acetoxy-aziridine precursor analogue, 2-(4-aceroxyphenyl1)-2-chloro-N-methyl-ethylammoniumchloride (Compound A) was synthesised, and found to be contraceptive in rats and to inhibit adrenal P450c11, like S2. An ethanolic extract from the plant, the active fraction from the plant, S2, and Compound A, the chemical analogue, were prepared and tested in the present study.

AFRIKAANSE OPSOMMING: Die studie vorm deel van 'n ondersoek van die sindroom van verlengde dragtigheid in skape en kontrasepsie in rotte, veroorsaak deur die Namibiese bos, Salsola tuberculatiformis Botsch. Bewyse was verkry vanaf studies met S. tubercuatisformis ekstrakte, toom dat verbinsings in bos adrenale steroidgenese in die rot versteur en die binding van die natuurlike substraat, deoksikortikosteroon, aan skaap adrenale sitochroom P450c11 verhoed. Swart beskryf die isolasie van een van die aktiewe verbindings in die bos, wat S2 genoem word. Daaar is gevind dat die S2 fraksie uit 'n mengsel van 'n hoogs labiele verbinding plus een of meer stabiele komponente, waarvan sinefrien een is, bestaan. In 'n waterige mediu is sinefrien 'n afbraak produk van die S2 fraksie. Derivatiserings studies het voorgestel dat die aktiewe komponent in S2 'n labiele hidroksie-feniel aziridien of die ooreenstemmende oop ketting voorloper mag wees. 'n Meer stabiele asetoksie-aziridien voorloper analoog, 2-(4-asetoksiefeniel)-2-chloro-N-metiel-etielammoniumchloried (Verbinding A) is gesintetiseer, en het kontraseptief getoets vir rotte en het adrenale P450c11 geïnhibeer, soos S2. 'n Etanoliese ekstrak van die plant, die aktiewe fraksie van die plant, S2, en Verbinding A, 'n analoog, is voorberei en getoets in die huidige studie.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/56009
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