Biomedical subjects

M Suganuma

Publications and source records attributed to M Suganuma.

At least 145 records · Page 8Linked to original sources

PubMed1984

Studies on olivoretins indicate a requirement for a free hydroxyl group for teleocidin B activity.

Three olivoretins, A, B and C (isolated from Streptoverticillium olivoreticuli), which are O-methylated teleocidin B isomers, were found to be biologically inactive. A fourth olivoretin, D, which has a free hydroxyl group and is identical to one of the four teleocidin B isomers, teleocidin B-4 (teleocidin B of Hirata) was biologically active. These findings indicate that the free primary hydroxyl group of teleocidin B isomers is necessary for activity. The effect on biological activity of the structural difference between des-O-methylolivoretin B (teleocidin B-1) and des-O-methylolivoretin C was also studied.

Animals↗

PubMed1984

Structure-activity studies on synthetic analogues (indolactams) of the tumor promoter teleocidin.

Synthetic analogues (indolactams) related to the tumor promoter teleocidin were synthesized chemically. Of four indolactam-Vs lacking the monoterpenoid moiety of native teleocidin, (-)-indolactam-V bound to the 12-O-tetradecanoylphorbol-13-acetate receptor in cell membranes and induced both adhesion of HL-60 cells and ornithine decarboxylase activity in mouse skin, although its effects were weaker than those of teleocidin. (+)-Indolactam-V and two isomers of epi-indolactam-V showed no induction of ornithine decarboxylase. These results indicate that the S,S configuration of native teleocidin at the isopropyl residue and the hydroxymethyl group is necessary for activity.

Animals↗

PubMed1983

Nakahara memorial lecture. New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin.

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)

Acrylamides↗

PubMed1982

Teleocidin from Streptomyces is a potent promoter of mouse skin carcinogenesis.

Teleocidin, isolated from Streptomyces mediocidicus ISP 5021, is an indole alkaloid. The teleocidin used was composed of teleocidin A, teleocidin B and their isomers. A hydrogenated derivative of teleocidin B, dihydroteleocidin B, was recently reported to have tumor promoting activity in vivo and various biological activities in vitro, with a specific activity comparable to that of 12-O-tetradecanoylphorbol-13-acetate (TPA). This paper describes the potent tumor promoting activity of the parent compound of dihydroteleocidins, teleocidin, on mouse skin in two-stage carcinogenesis. The tumor promoting activity was evaluated by measuring the incidence and yield of tumors, and by histological examination. Groups of mice were given a single application of 100 micrograms of 7,12-dimethylbenz[a]anthracene (DMBA) and then 2.5 micrograms of teleocidin twice weekly or the same dose of DMBA plus 2.5 micrograms of TPA twice weekly. Both groups showed 100% tumor incidence after 24 weeks, and the tumor yields were 4.0 tumors per mouse in the former group and 9.8 per mouse in the latter group in week 30. We confirmed, through this experiment, that teleocidin is as potent as TPA in in vivo two-stage carcinogenesis in mouse skin. These two structurally unrelated classes, indole alkaloid and phorbol ester, showed tumor promoting activity in almost the same range.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1982

The third class of new tumor promoters, polyacetates (debromoaplysiatoxin and aplysiatoxin), can differentiate biological actions relevant to tumor promoters.

Aplysiatoxin is a new class of potent tumor promoter and debromoaplysiatoxin may be a weak promoter. Aplysiatoxin and debromoaplysiatoxin showed the same potency on irritation of mouse ear and induction of ornithine decarboxylase activity on mouse skin, but debromoaplysiatoxin was much weaker than aplysiatoxin in induction of adhesion of HL-60 cells.

Animals↗

PubMed1982

Existence of an optimal dose of dihydroteleocidin B for skin tumor promotion.

The tumor-promoting effects of various doses of dihydroteleocidin B, a catalytically hydrogenated derivative of teleocidin B isolated from Streptomyces mediocidicus, were examined in a two-stage carcinogenicity test on mouse skin. Doses of 1.25, 2.5 and 5.0 micrograms of dihydroteleocidin B dissolved in 0.1 ml acetone were applied twice a week to 7,12-dimethylbenz[a]anthracene-initiated mouse skin for 30 weeks. The maximal cumulative tumor incidence, tumor yield, latent period for 50% cumulative tumor incidence (t50) and amount of promoter needed for 50% cumulative tumor incidence (D50) were used to assess tumor-promoting activity. A dose of 2.5 micrograms of dihydroteleocidin B had the maximal tumor-promoting activity. The optimal dose of dihydroteleocidin B for tumor-promoting activity coincided with the optimal dose for ornithine decarboxylase induction.

Alkaloids↗

PubMed1979