| Co-Investigator(Kenkyū-buntansha) |
OCHIAI Masahito Institute for Chemical Research, Kyoto University, 化学研究所, 助手 (50127065)
NODE Manabu Institute for Chemical Research, Kyoto University, 化学研究所, 助教授 (60027076)
FUJI Kaoru Institute for Chemical Research, Kyoto University, 化学研究所, 教授 (20027056)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1986: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1985: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
1) We designed a guideline for the development of new multifunctional anti-cancer agents based on much information on the thiol chemistry, DNA-binding drugs, the relationship between chemical structure and toxicity, and radiosencitizing chemistry of DNA.
2) According to our own guideline, we synthesized various thiazolidine-2-thiones, nitrofurazanes, 3-nitrotriazoles, and 2-nitroimidazoles, respectively. These new compounds and a Rabdosia diterpenoid, oridonin, were subjected to biological screening tests in vitro and in vivo system. From the results, the following facts were disclosed. Some thiazolidine-2-thione carboxylic acids having a weak immuno activity, exhibited fairly strong aldose reductase inhibition being concerned with the therapeutic agents for the chronic complications of diabetes. Nitrofurazanes, 3-nitrotriazoles, and 2-nitroimidazoles would be hopeful radiosencitizers in cancer radiotherapy. A tumor-inhibitor, oridonin showed an additive effect on the radiosencitizing activities of misonidazole to hypoxic cells. Thus, oridonin may be available for cancer radiotherapy.
3) In order to clarify active mechanism of a clinically useful anti-cancer drugs: camptotecin derivatives and bleomycin A2, polyamine-containing radiosencitizers, and benzo[C]-phenanthridine alkaloids, interaction between drugs and DNA was investigated utilizing the Tm measurement, UV difference spectum, and <^1H> - and <^(13)C> -NMR spectrum. It was revealed that benzo[C]-phenanthridine alkaloids clearly form strong charge-transfer complexes with the nucleic bases in double and and single strand DNA.
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