title: Synthesis and evaluation of water-soluble docetaxel prodrugs-docetaxel esters of malic acid.
abstract: The synthesis of docetaxel esters of malic acid is described. These compounds were found to have greatly improved water solubility and are stable in solution at neutral pH. The C2' modified compounds 2a-c and 3a-c behave as prodrugs, that is, docetaxel is generated upon exposure to human plasma, whereas the C7 and C2',7,10- l modified derivatives do not. 2'-dl-Malyl docetaxel sodium salt demonstrated enhanced antitumor activity in vitro when compared to docetaxel and showed the inhibitory effect on tumor growth in vivo.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Du
authors.forename: Lan
authors.initials: L
authors.lastname: Hong
authors.forename: Tongwei
authors.initials: T
authors.lastname: Yao
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Yang
authors.forename: Qiaojun
authors.initials: Q
authors.lastname: He
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000737:chemistry*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008293:Malates / Q000737:chemistry*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D010949:Plasma / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014867:Water
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004952:Esters; D008293:Malates; D011355:Prodrugs; D043823:Taxoids; D014867:Water; D000077143:Docetaxel