Studies on effects of forphenicinol on immune responses.

Ishizuka, Masaaki; Ishizeki, Seiji; Masuda, Tohru; Momose, Ayako; Aoyagi, Takaaki; Takeuchi, Tomio; Umezawa, Hamao

doi:10.7164/antibiotics.35.1042

Cited by 35 publications

(5 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As for the possible suppressive effect of monocytes (Bordignon et al 1982;Koren et al 1981), we found no correlation between NK activity and monocyte content in the MNC preparations concerned. Negative effect on the lymphocyte proliferation was previously observed in experimental animals (Ishizuka et al 1982a). …”

Section: Negative Effect On the Proliferative Responsementioning

confidence: 59%

“…Forphenicinol which did not inhibit the enzyme (IC50: 3501ag/ml) was found to enhance immune responses in mice (Ishizuka et al 1982a) and exhibit the antitumor effect on murine transplantable tumors as well as a protective effect on Pseudomonas infections by oral administration (Ishizuka et al 1982b). Forphenicinol was also shown to have extremely low toxicity in experimental animals (Ishizuka et al 1982b).…”

Section: N Kumano Et Almentioning

confidence: 99%

See 1 more Smart Citation

Changes in the immunological parameters after a single dose of forphenicinol, a new small molecular immunomodifier.

Kumano

Nakai

Ishikawa

et al. 1985

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

] is a derivative of forphenicine, an inhibitor of alkaline phosphatase discovered by Umezawa. In order to find an optimal dose, a single dose of the drug ranging from 10 to 600 mg per body was orally administered to a total of 55 patients (36 cancer, 13 tuberculosis, and 6 others). The possible changes in the percentages of the peripheral T and B lymphocytes, natural killer (NK) activity, and the proliferative response to phytohemaglutinin (PHA) were studied as Immunological parameters. A significant effect of forphenicinol was demonstrated in restoring the normal proportion of T and B cells, especially in those who had `low'-T and/or `high'-B before administration of the drug. No difference was found between cancer and tuberculosis. The mean percentage of T cells increased from the low initial level of 68.0 to 75.6 in cancer (n =12, p <0.05) or from 63.1 to 78.5 in tuberculosis (n=7, p <0.05), while that of B cells decreased from the high initial level of 34.6 to 26.9 in cancer (n = 7) or from 34.9 to 14.3 in tuberculosis (n =6, p <0.025). The effect of a single dose of the drug tended to disappear by day 8, a peak response being found on day 3 in most cases. With respect to this parameter, an optimal dose was found in a range from 60 to 100 mg. Forphenicinol was rather inhibitory on the NK activity, while it exerted diverse effect on the lymphocyte proliferation. No evidence of adverse effect was observed.-forphenicinol ; small molecular BRM ; T and B cells ; NK activity et al. 1982) is a derivative of forphenicine, an inhibitor of chicken intestine alkaline phosphatase (IC50 : 0.03 jig/ml) discovered by Umezawa and

show abstract

Section: Negative Effect On the Proliferative Responsementioning

confidence: 59%

Section: N Kumano Et Almentioning

confidence: 99%

Changes in the immunological parameters after a single dose of forphenicinol, a new small molecular immunomodifier.

Kumano

Nakai

Ishikawa

et al. 1985

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

“…The residue was purified on preparative silica gel TLC (chloroform -methanol, 10 : 1). Colorless needles of25 was obtained (272 mg, 52%): MP 97~98°C; "U NMR8 1.21 (9H, s, C(CH3)3), 4 A mixture of sodium salt of 20 (236 mg) and 4-(2-iodoethyl)morpholine (600 mg, prepared from 4-(2-chloroethyl)morpholine and sodium iodide), in THF (12 ml) and water (2 ml) was kept at room temperature for 1 day, and was concentrated. To the residue, water (50 ml) and triethylamine (0.1 ml) were added, and the morpholinoethyl ester was extracted with chloroform (15 mi x 5).…”

Section: Methodsmentioning

confidence: 99%

N-salicylidene derivatives of pirarubicin.

et al. 1989

Self Cite

View full text Add to dashboard Cite

The preparation and biological evaluation of Ar-salicylidene derivatives of pirarubicin are described. Pirarubicin was treated with various kinds ofaryl aldehydes. Most of compounds synthesized here were more active than pirarubicin in vitro. Someof themshowedsignificant prolongation of the survival period in experimental mice by oral administration. Interestingly, a derivative containing forphenicine exhibited the broadest dose-response range by intraperitoneal administration. In the search for useful and orally absorbable analogues, we found that iV-salicylidene derivatives of pirarubicin were therapeutically superior to doxorubicin in murine models. Someof them showed the possibility of being orally absorbable agents in in vivo tests.Wewish to demonstrate here the synthesis of sixteen TV-salicylidene derivatives (3~5 and 7~19) of pirarubicin (1) and their biological evaluation in vivo and in vitro. Chemistry Pirarubicin (1) was treated with various kinds of aryl aldehydes in chloroform or in a mixture of chloroform and methanol. At first, 1 was converted into its iV-salicylidene derivative (3) by treatment with salicylaldehyde in a good yield after chromatographic separation on silica gel with chloroformmethanol containing triethylamine. The Schiff base-methine proton of 3 in 2H NMRspectrum resonated clearly at d 8.35. A similar treatment of 1 with benzaldehyde did not afford a benzylidene derivative of 1 because of the lability of the product. 7V_Salicylideneadriamycin (2) was prepared by Arcamoneet alP as an intermediate of the synthesis of doxorubicin from daunorubicin, but they did not describe any biological data of 2. Compound3 was acylated with valeryl and decanoyl chlorides in pyridine and re-salicylidenated to give 14-0-valeryl and 14-0-decanoyl derivatives (4 and 5). To comparethe biological activities of Schiff base derivative (3) with 7V-alkyl derivative, compound6 was prepared by Borch reduction of 1 with salicylaldehyde and NaB(CN)H3in acidic medium. Since the reductive alkylation of the amino group of 1 competed with the reduction of the 13-carbonyl group, the yield of 6 was poor.iV-Salicylidene derivatives of 1 having electron-donating group(s) on the aryl ring were synthesized.Reaction of 1 with substituted-aldehydes (3-, 4-and 5-hydroxy, 3,4-dihydroxy, 4-and 5-methoxy-A part of this work was presented at the 243rd JARAResearch Meeting in Tokyo on Dec. 13. 1988.

show abstract

“…1). This compound exhibits immunomodulator 8 and anti-cancer (Ehrlich and IMC carcinomas) 9 properties itself or in combination with other anticancer drugs. 10,11 It can also be used for treatment of respiratory 12 and other medical problems 13,14 whereas (R)-forphenicinol is nearly inactive.…”

Section: Introductionmentioning

confidence: 99%