Synthesis of derivatives of NK109, 7-OH benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties |
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Authors: | Nakanishi T Masuda A Suwa M Akiyama Y Hoshino-Abe N Suzuki M |
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Affiliation: | Pharmaceuticals Group, Nippon Kayaku Company, Ltd., Tokyo, Japan. t_naka@fra.allnet.ne.jp |
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Abstract: | The N5-C6 double bond of NK109 (an antitumor benzo[c]phenanthridine alkaloid) is easily reduced under biological environment. To suppress the inactivation caused by reduction, we synthesized 5-, 6-, and 8-substituted NK109. 5-Substituted derivatives (4a-c) were reduced more easily than NK109. 6-Substituted ones (10a-f) inhibited biological reduction, but showed weak cytotoxic activity. 8-O-Substituted ones (13a-h), especially 8-O-hydroxyethyl NK109 (13d), suppressed biological reduction and exhibited strong cytotoxic activity. |
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