STRUCTURE-ACTIVITY RELATIONS OF TERATOGENIC NATURAL-PRODUCTS

Mammalian ingestion of jervane, solanidane, and spirosolane steroidal alkaloids produces craniofacial congential malformations in offspring upon administration during the primitive streak/neural plate developme ntal phase. Structure-terata studies have shown that hamster teratogen icity induced by steroidal alkaloids is primarily related to the prese nce of C-5, C-6 unsaturation and secondarily to the molecular configur ation at C-22 (spirosolanes and solanidanes). Teratogenic potencies of jervanes and solanidanes are appreciably higher than those of spiroso lanes whereas the potency of jervanes is generally greater than that o f solanidanes. The enhanced teratogenicity of functionalized steroidal alkaloids implies that their amphiphilic nature may be important in f acilitating their passage of the embryonic membrane.