Synthesis and evaluation of antitumor activity of novel 1,4-naphthoquinone derivatives (IV).
1,4-Naphthoquinones are widely distributed in nature and many clinically important antitumor drugs containing a quinone moiety, such as anthracyclines, mitoxantrones and saintopin, show excellent anticancer activity. In this study, 2- or 6-substituted 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) and 5,8-dihydroxy-1,4-naphthoquinone (DHNQ) derivatives were synthesized, and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor activity was also assessed in mice bearing S-180 cells in the peritoneal cavity. In comparison with the DMNQ derivatives, the DHNQ derivatives exhibited more potent bioactivities than the DMNQ derivatives against both L1210 and P388 cells in vitro and S-180 cells in vivo. The ED50 values of the DHNQ derivatives against P388 cells were in the range of 0.18-1.81 microg/mL whereas those of the DMNQ derivatives were in the range of 0.26-40.41 microg/mL. The T/C (%) values of the DHNQ derivatives, 8, 17, 18, 19, and 20, were found to be comparable to or even better than that of adriamycin. It was also observed that the 2-substituted derivatives (8, 19, 20) showed better antitumor activity than the 6-substituted derivatives (7, 17, 18) in the mice bearing S-180 cells in the peritoneal cavity.
Kim
Bok Hee
BH
College of Engineering, Chosun University, Gwangju 501-759, Korea.
Yoo
Jikang
J
Park
Si-Hyun
SH
Jung
Jae-Kyung
JK
Cho
Hoon
H
Chung
Yongseog
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009285:Naphthoquinones; C005503:naphthazarin; C063002:2,3-dimethoxy-1,4-naphthoquinone