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Biomedical subjects

Y Hitotsuyanagi

Publications and source records attributed to Y Hitotsuyanagi.

14 recordsLinked to original sources

The cytotoxicity and chemical constituents of the hexane fraction of Typhonium flagelliforme (Araceace).

The plant, Typhonium flagelliforme (Araceae), commonly known as the "rodent tuber" in Malaysia, is often used as an essential ingredient of herbal remedies for alternative cancer therapies. The hexane extract of this plant was evaluated for cytotoxic activity against in vitro culture on P388 murine leukaemia cells and showed weak IC(50) of 15 microg/ml. The partial chemical constituents were identified as methyl esters of hexadecanoic acid, octadecanoic acid, 9-octadecenoic acid and 9,12-octadecadienoic acid. In addition, several common aliphatics were identified as dodecane, tridecane, tetradecane, pentadecane, hexadecane, heptadecane, octadecane, nonadecane and eicosane. The unique methyl ester of 13-phenyltridecanoic acid was isolated and positively identified using spectroscopic methods. None of the identified compounds showed or are known to have cytotoxic behaviour.

Animals↗

4-Aza-2,3-dehydro-4-deoxypodophyllotoxins: simple aza-podophyllotoxin analogues possessing potent cytotoxicity.

4-Aza-2,3-dehydro-4-deoxypodophyllotoxin analogues 3a-n were synthesized through quinolines 2a-n. Comparison of their cytotoxicity against P-388 leukemia cells revealed that the steric effects of the ring B substituents on the activity are greater than the electronic effects, while the presence of a methoxy group on the ring E is not essential to exhibit potent cytotoxicity. Analogues 3a and 3b proved to be more than twice as cytotoxic as natural podophyllotoxin (1).

Antineoplastic Agents, Phytogenic↗

[Antitumor compounds isolated from higher plants].

A lot of anticancer agents have been isolated from natural sources, especially from microorganisms and plants. However, there is no special type of compounds for cancer therapy. Various types of substances are effective for various types of cancers and tumors: for instance, alkaloids, lignans, terpenes and steroids, etc. In this report, the authors will describe especially about higher plants.

Alkaloids↗

Cytotoxic quassinoids from Simaba cedron.

Four new quassinoids, cedronolactones A-D (1-4), together with nine known compounds, simalikalactone D (5), chaparrinone (6), chaparrin (7), glaucarubolone (8), glaucarubol (9), samaderine Z (10), guanepolide (11), ailanquassin A (12), and polyandrol (13), were isolated from the wood of Simaba cedron. The chemical structures of 1-4 were elucidated on the basis of their chemical and spectral properties. Cedronolactone A (1) was shown to exhibit a significant in vitro cytotoxicity (IC50 0.0074 microg/mL) against P-388 cells.

Alkaloids↗

Preparation and cytotoxicity of cyclic hexapeptides, RA derivatives.

Several aromatic ring substituent modified RA derivatives were prepared from RA-VII (1), RA-V (8) and RA-II (11), and evaluated for cytotoxicity against P388 leukemia and KB cells. In terms of IC50 values, the C zeta methoxyl group of Tyr-3 greatly influenced the activities, while the substituents at the C zeta position of Tyr-6 were less important. One of the derivatives, Tyr-6-C zeta-deoxyRA-V (9, P388, IC50, 0.0025 micrograms/ml) was nearly as active as RA-VII (1, 0.0013 micrograms/ml), and also expressed promising anti-P388 in vivo activity (test/control = 171%, at 25 mg/kg).

Animals↗

Studies on RA derivatives. V. Synthesis and antitumor activity of Ala2-modified RA-VII derivatives.

A number of RA-VII derivatives having various amino acids including proline (6), pipecolic acid (11), norvaline (12), ornithine (14), aspartic acid (15) and methionine (20) in place of Ala2 have been synthesized from RA-X methyl ester (3) and evaluated for cytotoxicity to P388 leukemia and KB cells in vitro. Comparison of the cytotoxicity of these compounds suggests that the polarity and the length of the 2nd amino acid residue affect the activity. An NMR study revealed that, in solution, 6 and 11 are locked in one conformational state, corresponding to conformer A of RA-VII.

Animals↗

Similar, potent tumor-promoting activity of all isomers of teleocidins A and B in a two-stage carcinogenesis experiment on the skin of CD-1 mice.

Teleocidin, isolated from mycelia of Streptomyces mediocidicus is a mixture of two teleocidin A isomers with molecular weights of 437 (A-1 and A-2) and four teleocidin B isomers with molecular weights of 451 (B-1, B-2, B-3, and B-4). Previously we found that each purified isomer of teleocidins A and B had approximately the same activity as teleocidin in an irritant test on mouse ear, in inductions of ornithine decarboxylase in mouse skin and adhesion of human promyelocytic leukemia (HL-60) cells, and in inhibition of the specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to a mouse skin particulate fraction. This paper reports the strong activation of protein kinase C in vitro by each isomer of teleocidins A and B at a concentration of 1 microgram/ml. Detailed studies on the potent tumor promoting activities of the two teleocidin A isomers and four teleocidin B isomers in a two-stage carcinogenesis experiment on mouse skin are also reported, including histological findings on the tumors. Treatment of mice with 100 micrograms of 7,12-dimethylbenz(a)anthracene and then 2.5 micrograms of any one of the six isomers of teleocidins A and B twice a week induced tumors in 80.0 to 91.7% of the mice with 2.8 to 5.2 tumors/mouse in week 30. Scarcely any tumors developed in groups treated with 7,12-dimethylbenz(a)anthracene or any one of the isomers of teleocidins A or B alone. The percentages of incidences of mice bearing papillomas and carcinomas in the six groups treated with 7,12-dimethylbenz(a)anthracene plus one isomer of teleocidins A or B were 90.9 to 98.3% and 1.7 to 9.1%, respectively. These results indicate that all of the isomers of teleocidins A and B have potent tumor promoting activity on mouse skin, irrespective of the structural differences between teleocidins A-1 and A-2, and among the four isomers of teleocidin B. The structure-activity relationship of teleocidins A and B is discussed on the basis of our recent results. Based on the structures of related compounds, we propose a revised numbering system for compounds of the teleocidin class.

9,10-Dimethyl-1,2-benzanthracene↗

Des-O-methylolivoretin C is a new member of the teleocidin class of tumor promoters.

Des-O-methylolivoretin C, a demethylated form of olivoretin C, is a naturally occurring compound in Streptomyces mediocidicus and Streptoverticillium olivoreticuli. Des-O-methylolivoretin C is a regioisomer of teleocidin B, which has the same activity as teleocidin. The tumor-promoting activity of des-O-methylolivoretin C was studied in a two-stage carcinogenesis experiment on mouse skin in comparison with that of teleocidin. Treatments with 7,12-dimethylbenz[a]anthracene (DMBA) plus des-O-methylolivoretin C and DMBA plus teleocidin induced tumors in 63.3% and 84.6% of the mice, respectively, in week 30. The difference in the tumor-promoting activities of des-O-methylolivoretin C and teleocidin is presumably related to the regioisomeric difference in the cyclohexene ring.

9,10-Dimethyl-1,2-benzanthracene↗

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↗