title: Nakahara memorial lecture. New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin.
abstract: Teleocidin and aplysiatoxin, which are structurally different from 12-O-tetradecanoylphorbol-13-acetate (TPA), were found to be potent tumor promoters in two-step mouse skin carcinogenesis. The class of teleocidin includes dihydroteleocidin B, teleocidin, and lyngbyatoxin A. Teleocidin, which is a mixture of 93% teleocidin A and 7% teleocidin B, was isolated from Streptomyces mediocidicus as a strong skin irritant. Teleocidin A consists of C-14S-teleocidin A and C-14R-teleocidin A. One teleocidin A-isomer corresponds to lyngbyatoxin A, which was isolated from the blue-green alga, Lyngbya majuscula. Teleocidin B has four isomers, C-14, C-17-diastereomers. The two teleocidin A-isomers and three of the teleocidin B-isomers (all but one, which was obtained in too low yield) were shown to be biologically active and also potent tumor promoters. Synthetic analogues (indolactams) of teleocidin were obtained and their structure-activity relations were examined by several biological tests. The finding that only (-)-indolactam-V was active showed that the S, S configuration of native teleocidin was necessary for expression of the activity. The class of aplysiatoxin, which was isolated from the blue-green alga, L. majuscula, includes debromoaplysiatoxin, aplysiatoxin, bromoaplysiatoxin, and oscillatoxin A (nordebromoaplysiatoxin). The former three were potent tumor promoters, while oscillatoxin A was a moderate one. Dibromoaplysiatoxin, which is a chemically brominated derivative of debromoaplysiatoxin, in addition to aplysiatoxin and bromoaplysiatoxin, possessed the same promoting activity as that of oscillatoxin A.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000178:Acrylamides; D000818:Animals; D002273:Carcinogens; D003064:Cnidarian Venoms / Q000633:toxicity*; D006801:Humans; D008235:Lyngbya Toxins / Q000633:toxicity*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000095702:Polyether Toxins
chemical_list: D000178:Acrylamides; D002273:Carcinogens; D003064:Cnidarian Venoms; D008235:Lyngbya Toxins; C022176:teleocidins; C017179:debromoaplysiatoxin; C006610:aplysiatoxin; C010272:palytoxin; D000095702:Polyether Toxins