title: Design, Synthesis, and Biological Evaluation of a Novel Water-soluble Prodrug of Docetaxel with Amino Acid as a Linker.
abstract: The synthesis and preliminary evaluation of derivatives of docetaxel with novel amino acid as a linker named as LK-193˜LK-196 was described. The C2'-modified compound LK-196 behaves as a prodrug; that is, docetaxel is generated upon exposure to human plasma. The compound was also found to have greatly improved water solubility. The pharmacodynamic results showed LK-196 had the self-evident inhibitory effect on tumor growth in vivo, which is a promising candidate for further biological evaluation.
authors.affiliation: School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ma
authors.affiliation: R&D Department, Jiangsu Nhwa Luokang Pharmaceutical Corporation Ltd., Xu Zhou, 221000, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: R&D Department, Jiangsu Nhwa Luokang Pharmaceutical Corporation Ltd., Xu Zhou, 221000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Qingeng
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D015195:Drug Design; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D043823:Taxoids; D014867:Water; D000077143:Docetaxel
keywords: Prodrug of docetaxel; biological evaluation; synthesis; water-soluble