Structure-activity studies of trichothecenes: cytotoxicity of analogues and reaction products derived from T-2 toxin and neosolaniol.

Forty-two analogues and reaction products derived from T-2 toxin or neosolaniol were assayed for their cytotoxicity to cultured mouse lymphoma cells. Structure-activity relationships confirmed the stereospecific nature of the cytotoxic action of T-2. Cytotoxicity was particularly susceptible to changes at C3, C4, C9, and C10 but was relatively unaffected by changes at C8, which appears to represent a region of steric tolerance in the interaction of T-2 with a cellular constituent. The most potent compounds were T-2, diacetoxyscirpenol, and a series of C8 ester analogues 11 and 31-35.

The synthesis and pharmacology of some 1,4,5,6-tetrahydropyrimidines.

1. Several 1- and 2-substituted, and 1,2-disubstituted, 1,4,5,6-tetrahydropyrimidines have been prepared and their toxicological and pharmacological properties have been investigated.2. In general the compounds were neuromuscular blocking agents with the monosubstituted members of the series showing a depolarizing type of activity and the disubstituted compounds a non-depolarizing type.3. The toxicity to mice of some of the monosubstituted compounds was increased by pretreatment of the animals with SKF 525A, but the toxicity of the disubstituted compounds was unaffected.4. The results obtained with these compounds are not at variance with a suggestion made previously that nicotinic action at the neuromuscular junction can result from an interaction between drug and receptor at two points separated by about 4 A.