title: Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents.
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.
authors.affiliation: Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.forename: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Tzu-Hsuan
authors.initials: TH
authors.lastname: Chen
authors.forename: Po-Cheng
authors.initials: PC
authors.lastname: Chiang
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Shao-Chun
authors.initials: SC
authors.lastname: Wang
authors.forename: Bill
authors.initials: B
authors.lastname: Spohn
authors.forename: Mien-Chie
authors.initials: MC
authors.lastname: Hung
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Lee
authors.forename: Fang-Chen
authors.initials: FC
authors.lastname: Lee
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D043823:Taxoids