Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant-taxoid conjugates as novel cytotoxic agents

作者：Nakagawa Goto Kyoko; Yamada Koji; Nakamura Selkou; Chen Tzu Hsuan; Chiang Po Cheng; Bastow Kenneth F; Wang Shao Chun; Spohn Bill^*; Hung Mien Chie; Lee Fang Yu; Lee Fang Chen; Lee Kuo Hsiung

来源：Bioorganic & Medicinal Chemistry Letters, 2007, 17(18): 5204-5209.

DOI：10.1016/j.bmcl.2007.06.083

• conjugation
• paclitaxel
• antioxidant
• cytotoxicity

Various dietary antioxidants, including vitamins, flavonoids, curcumin, and a coumarin, were conjugated with paclitaxel (1) through an ester linkage. The newly synthesized compounds were evaluated for cytotoxic activity against several human tumor cell lines as well as the corresponding normal cell lines. Interestingly, most tested conjugates selectively inhibited the growth of 1 A9 (ovarian) and KB (nasopharyngeal) tumor cells without activity against other cell lines. Particularly, conjugates 16 and 20 were highly active against 1 A9 (ED50 value of 0.005 mu g/mL) as well as KB (ED50 values of 0.005 and 0.14 mu g/mL, respectively) cells. Compound 22b, the glycinate ester salt of vitamin E conjugated with 1, appears to be a promising lead for further development as a clinical trial candidate as it exhibited strong inhibitory activity against Panc-1 (pancreatic cancer) with less effect on the related E6E7 (normal) cell line.

• 出版日期2007-9-15
• 单位中国医科大学