STRUCTURAL RELATIONSHIPS AND DEVELOPMENTAL TOXICITY OF SOLANUM ALKALOIDS IN THE FROG EMBRYO TERATOGENESIS ASSAY-XENOPUS

Solanum plants produce potentially toxic alkaloids. As part of a program to improve safety of plant-derived foods such as potatoes, we examined the relative embryotoxicities of 13 structurally different compounds using the frog embryo teratogenesis assay-Xenopus (FETAX). Our purpose was to better understand structural features governing the developmental toxicology of these compounds. We measured the minimum concentrations needed to inhibit growth of the embryos, the median lethal concentration of 96-h exposure (96-h LC50), and the concentration inducing gross terata in 50% of the surviving animals [96-h EC50 (malformation)]. The following glycoalkaloids produced concentration-response curves: alpha-chaconine, alpha-solanine, solasonine, and alpha-tomatine. All compounds were tested at equimolar (0.005 and 0.015 mM) concentrations in order to develop a relative potency scale. The data showed that (a) glycoalkaloids are more toxic than corresponding aglycons lacking the carbohydrate groups, (b) for glycoalkaloids, the nature of the carbohydrate strongly influences potency, (c) the nitrogen of the steroid is required for teratogenicity, (d) the orientation of the unshared electron pair associated with the nitrogen atom does not affect potency, and (e) the presence of nitrogen in rings of non-steroidal alkaloids such as atropine, scopolamine, and ergonovine does not impart teratogenicity. The observed structural effects should facilitate predicting developmental toxicities of compounds of dietary interest without the use of live animals and provide information to guide selection of potato plants with a low content of specific toxic alkaloids. The possible significance of the results to food safety is discussed.