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.

Abstract

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.

• Authors: Jikang Yoo, Hyun-Suk Choi, Cheol-Hee Choi, Yongseog Chung, Bok Hee Kim, Hoon Cho
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 31 Issue 2 Pg. 142-7 (Feb 2008) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 18365681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Naphthoquinones
• Tetrazolium Salts
• Thiazoles
• thiazolyl blue

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Drug Screening Assays, Antitumor
• Leukemia L1210 (drug therapy)
• Leukemia P388 (drug therapy)
• Male
• Mice
• Mice, Inbred ICR
• Naphthoquinones (chemical synthesis, pharmacology)
• Neoplasm Transplantation
• Sarcoma 180 (drug therapy)
• Structure-Activity Relationship
• Tetrazolium Salts
• Thiazoles