title: Antitumor agents. 256. Conjugation of paclitaxel with other antitumor agents: evaluation of novel conjugates as cytotoxic agents.
abstract: Sixteen different taxoid conjugates were prepared by linking various anticancer compounds, including camptothecin (CPT), epipodophyllotoxin (EP), colchicine (COL), and glycyrrhetinic acid (GA), at the 2'- or 7-position on paclitaxel (TXL, 1) through an ester, imine, amine, or amide bond. Newly synthesized conjugates were evaluated for cytotoxic activity against replication of several human tumor cell lines. Among them, TXL-CPT conjugates, 8-10, were more potent than TXL itself against the human prostate carcinoma cell line PC-3 (ED(50)=14.8, 3.1, 19.4nM compared with 55.5nM), and conjugate 10 was also 8-fold more active than TXL against the LN-CAP prostate cancer cell line. These compounds also possessed anti-angiogenesis ability as well as lower inhibitory effects against a normal cell line (MRC-5). Thus, conjugates 8-10 are possible antitumor drug candidates, particularly for prostate cancer.
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: Seikou
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Alexander
authors.initials: A
authors.lastname: Nyarko
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Peng
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: D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008297:Male; D015394:Molecular Structure; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D003603:Cytotoxins; D043823:Taxoids; D017239:Paclitaxel