Structure–activity relationships for osteolathyrism. III. Substituted thiosemicarbazides

✍ Scribed by Douglas A. Dawson; T. Wayne Schuitz; Leslie L. Baker; Anuradha Mannar

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 562 KB
• Volume: 10
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.2550100111

✦ Synopsis

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 E C ~~) 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 L C ~~) or for the mortality/malformation index (LC~D/EC~,,) due to the limited number of chemicals eliciting each lethal mode of action. 0 IWJ by John Wiley & Sons, Ltd.