Synthesis and evaluation of antitumor activity of novel 2-[Nmethyl-N-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-diacyloxy-1,4-naphthoquinones.
A series of nine new compounds bridged by acyl groups at the 5,8-dihydroxyl group of DHNQ were synthesized and their cytotoxic activity against L1210 and P388 cancer cells was examined. Their antitumor action in mice bearing S-180 cells in the peritoneal cavity was also assessed. Increasing the size of the acyl group (compounds 7-9) up to propyl increased the antitumor activity (T/C value), whereas the cytotoxicity of these compounds was comparable against L1210 (lymphocytic leukemia) and P388 (lymphoid neoplasm) cancer cells. Further increasing in the chain length (compounds 11-15) decreased the potency. Thus, acyl group chains of three carbon atoms is optimal for antitumor activity. The most potent compound of this series was 2-[N-methyl-N-(4-methyl-1,3-benzothiazol-2-yl)aminomethyl]-5,8-dipropylcarbonyloxy-1,4-naphthoquinone (compound 9) with a T/C (%) value of 354.
Yoo
Jikang
J
Department of Polymer Science & Engineering, Chosun University, Gwangju 501-759, Korea.
Choi
Hyun-Suk
HS
Choi
Cheol-Hee
CH
Chung
Yongseog
Y
Kim
Bok Hee
BH
Cho
Hoon
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D009368:Neoplasm Transplantation; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue