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.
Anderson
D W
DW
Chemical Defence Establishment, Salisbury, Wiltshire, United Kingdom.
Black
R M
RM
Lee
C G
CG
Pottage
C
C
Rickard
R L
RL
Sandford
M S
MS
Webber
T D
TD
Williams
N E
NE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D004354:Drug Screening Assays, Antitumor; D008223:Lymphoma / Q000188:drug therapy; D051379:Mice; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship; D013605:T-2 Toxin; D014255:Trichothecenes / Q000138:chemical synthesis* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012717:Sesquiterpenes; D014255:Trichothecenes; C016009:neosolaniol; D013605:T-2 Toxin