title: Water-soluble prodrugs of paclitaxel containing self-immolative disulfide linkers.
abstract: A new series of disulfide-containing prodrugs of paclitaxel were designed, synthesized and evaluated against 6 cancer cell lines. Some of these prodrugs exhibited nearly equal or slightly better anticancer activity when compared to that of paclitaxel. These prodrugs contain water-soluble groups such as amino, carboxyl, hydroxyl, amino acids, etc., and exhibited 6-140 fold increase in aqueous solubility when compared to paclitaxel. One of these prodrugs exhibited improved water solubility, better in vitro anticancer activity and significantly superior oral bioavailability in mice when compared to those of paclitaxel. Thus, we have identified a very promising lead compound for further optimization and evaluation as a potentially bioavailable water-soluble prodrug of paclitaxel.
authors.affiliation: Medicinal Chemistry Division, Piramal Enterprises Limited, 1-Nirlon Complex, Goregaon East, Mumbai 400063, India.
authors.forename: Machhindra
authors.initials: M
authors.lastname: Gund
authors.forename: Amit
authors.initials: A
authors.lastname: Khanna
authors.forename: Nauzer
authors.initials: N
authors.lastname: Dubash
authors.forename: Anagha
authors.initials: A
authors.lastname: Damre
authors.forename: Kishore S
authors.initials: KS
authors.lastname: Singh
authors.forename: Apparao
authors.initials: A
authors.lastname: Satyam
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry* / Q000378:metabolism; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000378:metabolism
chemical_list: D004220:Disulfides; D011355:Prodrugs; D014867:Water; D017239:Paclitaxel