Antitumor Agents. 258. Syntheses and Evaluation of Dietary Antioxidant--taxoid Conjugates As Novel Cytotoxic Agents

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2007 Jul 24

PMID 17643301

Citations 15

Authors

Kyoko Nakagawa-Goto

Koji Yamada

Seikou Nakamura

Tzu-Hsuan Chen

Po-Cheng Chiang

Kenneth F Bastow

Shao-Chun Wang

Bill Spohn

Mien-Chie Hung

Fang-Yu Lee

Fang-Chen Lee

Kuo-Hsiung Lee

Affiliations

Soon will be listed here.

Abstract

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 1A9 (ovarian) and KB (nasopharyngeal) tumor cells without activity against other cell lines. Particularly, conjugates 16 and 20 were highly active against 1A9 (ED(50) value of 0.005 microg/mL) as well as KB (ED(50) values of 0.005 and 0.14 microg/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.

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