Synthesis of derivatives of NK109, 7-OH benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties.
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.
Nakanishi
T
T
Pharmaceuticals Group, Nippon Kayaku Company, Ltd., Tokyo, Japan. t_naka@fra.allnet.ne.jp
Masuda
A
A
Suwa
M
M
Akiyama
Y
Y
Hoshino-Abe
N
N
Suzuki
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D053119:Benzophenanthridines; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010617:Phenanthridines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D053119:Benzophenanthridines; C108284:NK 109; D010617:Phenanthridines