Antitumor agents. 258. Syntheses and evaluation of dietary antioxidant--taxoid conjugates as novel cytotoxic agents.
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.
Nakagawa-Goto
Kyoko
K
Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Yamada
Koji
K
Nakamura
Seikou
S
Chen
Tzu-Hsuan
TH
Chiang
Po-Cheng
PC
Bastow
Kenneth F
KF
Wang
Shao-Chun
SC
Spohn
Bill
B
Hung
Mien-Chie
MC
Lee
Fang-Yu
FY
Lee
Fang-Chen
FC
Lee
Kuo-Hsiung
KH
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*
D000970:Antineoplastic Agents; D000975:Antioxidants; D043823:Taxoids