Structure–activity relationships for osteolathyrism. III. Substituted thiosemicarbazides
Autor: | L L Baker, Terry W Schultz, Douglas A. Dawson, A Mannar |
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Rok vydání: | 1990 |
Předmět: |
Quantitative structure–activity relationship
Chemical Phenomena Lathyrism Stereochemistry Substituent Biological activity Biology Toxicology medicine.disease Osteolathyrism Semicarbazides Chemistry Structure-Activity Relationship Xenopus laevis chemistry.chemical_compound Teratogens chemistry Molar refractivity medicine Animals Structure–activity relationship Bone Diseases Mode of action |
Zdroj: | Journal of Applied Toxicology. 10:59-64 |
ISSN: | 1099-1263 0260-437X |
DOI: | 10.1002/jat.2550100111 |
Popis: | Eight substituted thiosemicarbazides were assayed for their toxicity and teratogenicity using early embryos of Xenopus laevis. Results of the 96-h static tests on seven 4-position alkyl substituents were used for quantitative structure-activity relationship (QSAR) analyses, with thiosemicarbazide as the parent compound. The compounds induced malformations via the connective tissue defect osteolathyrism. Teratogenicity (log EC50) was negatively correlated with molar refractivity, suggesting that steric inhibitions were important in explaining the variations in biological activity due to changes in the 4-position substituent. It appeared that there were two separate modes of lethal action, one associated with the ring-containing substituents and the other with straight-chain substituents. However, QSARs were not developed for embryolethality (log LC50) or for the mortality/malformation index (LC50/EC50) due to the limited number of chemicals eliciting each lethal mode of action. |
Databáze: | OpenAIRE |
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