Minoru Toriya

New neplanocin analogues. III: 6'R-configuration is essential for the antiviral activity of 6'-C-methyl-3-deazaneplanocin A's

(6′ R )- and (6′ S -6′- C -methyl-3-deazaneplanocin As were synthesized from D-ribose as anti-RNA virus agents. Of these compounds, (6′ R )-6′- C -methyl-3-deazaneplanocin A ( 4b ) showed the greatest anti-RNA virus activity in vitro . It was found that the 6′ R -configuration was essential for the antiviral activity of 6′- C -methylneplanocin A derivatives.

Antitumor Effect of Photodynamic Therapy with Zincphyrin, Zinc-coproporphyrin III, in Mice

We studied the antitumor effects of photodynamic therapy (PDT) with Zincphyrin, coproporphyrin III with zinc, derived from Streptmyces sp. AC8007, in vitro and in vivo. The photokilling effect of Zincphyrin in the presence of 0.78-100 μg/ml with visible light of 27.2 mW·min/cm2 for 10min was lower than the hematoporphyrin (Hp) used as a control with L5178Y or sarcoma-180 cells. On the other hand, Zincphyrin apparently reduced tumor growth after intraperitoneal injenction at doses of 12.5-50 mg/kg with light irradiation of 75.48 mW·min/cm2 for 10 min in sarcoma-180-bearing mice. Although no mice treated with Zincphyrin died, Hp did cause the death of mice. In B-16 melanoma-bearing mice, both Zincphyrin and Hp had a similar phototherapic effect. Further improvement of the phototherapic effect was observed with the continuous administration of Zincphyrin at 12.5 mg/kg per day for 3 days. The concentration of Zincphyrin in the serum reached a maximum level of 16 μg/ml within 20 min, and the concentration remained at 4.2 μg/ml at 1 hour after the onset of treatment, indicating its rapid action in the body. No animals died after the intraperitoneal administration of Zincphyrin at 100 mg/kg plus exposure to light of 10 mW·min/cm2 for 2 hours, and the body weight of the mice did not decrease. In contrast, all animals receiving 100 mg/kg of Hp under the same conditions died. These results indicate that Zincphyrin would be a useful photosensitizer with low phototoxicity.

New Neplanocin Analogues. V. A Potent Adenosylhomocysteine Hydrolase Inhibitor Lacking Antiviral Activity. Synthesis And Antiviral Activity Of 6″-Carboxylic Acid Derivatives Of Neplanocin A 1

Abstract The 6′-carboxylic acid derivative of neplanocin A 3 was synthesized from NPA, and was converted to the corresponding methyl ester 4 and amides 5 and 6. These were evaluated for their anti-RNA-virus activities. Of the derivatives synthesized, only 5 was active against RNA viruses within the concentration range of 0.14-4.88 μg/mL. Compounds 3 and 5 showed a potent inhibitory effect on S-adenosylhomocysteine (AdoHcy) hydrolase from rabbit erythrocytes. Although a close correlation between the inhibitory effect of adenosine analogues on AdoHcy hydrolase and their antiviral potency has been demonstrated, 3 did not show any anti-RNA-virus activities. 1This paper constitutes part 146 of Nucleosides and Nucleotides. Part 145. Shuto, S.; Haramuishi, K.; Matsuda, A. Tetrahedron Lett. Submitted.