Design, synthesis and biological evaluation of novel fluorinated docetaxel analogues.
A series of novel fluorinated docetaxel analogues have been synthesized and evaluated in vitro and in vivo. Incorporated one, two or three fluorine atom(s) either at both meta position on C-2 benzolate and 3'-N-tert-butyloxyl group or only at 3'-N-tert-butyloxyl group has resulted in potent analogues which have comparable or superior in vitro and in vivo cytotoxicity to docetaxel. Among them, compounds 14d and 14e have displayed more potent cytotoxicity than docetaxel both in human cancer cell line SK-OV-3 in vitro and in human non-small cell lung cancer A549 xenografts in vivo. Preliminary data show that compound 14a has reduced acute animal toxicity in mice compared with docetaxel.
Department of Chemistry of Natural Drugs, School of Pharmacy, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
Hong-Fu
HF
Lu
Xun
X
Sun
Liang
L
Xu
Li-Guang
LG
Lou
Guo-Qiang
GQ
Lin
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D000077143:Docetaxel; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005461:Fluorine; D006801:Humans; D051379:Mice; D043823:Taxoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D005461:Fluorine