title: Design, synthesis and initial biological evaluation of a novel pladienolide analog scaffold.
abstract: A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first totally synthetic analog of this macrolide that shows biological activity. Our novel synthetic strategy enables the rapid synthesis of other new analogs of pladienolide in order to develop selective anticancer lead compounds.
authors.affiliation: Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, U.S.A. ; Tel: 901 595 3928.
authors.forename: Mahesh Kumar
authors.initials: MK
authors.lastname: Gundluru
authors.forename: Alan
authors.initials: A
authors.lastname: Pourpak
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cui
authors.forename: Stephan W
authors.initials: SW
authors.lastname: Morris
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Webb