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7218918 
Journal Article 
Water-soluble prodrugs of paclitaxel containing self-immolative disulfide linkers 
Gund, M; Khanna, A; Dubash, N; Damre, A; Singh, KS; Satyam, A; , 
2015 
Yes 
Bioorganic & Medicinal Chemistry Letters
ISSN: 0960-894X
EISSN: 1464-3405 
PERGAMON-ELSEVIER SCIENCE LTD 
OXFORD 
122-127 
25466201 
WOS:000345581600024 
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. (C) 2014 Elsevier Ltd. All rights reserved.