title: Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents.
abstract: Modifications of the B-segment of HTI-286 (2) produced a class of analogs incorporating heteroatom-substituents. The structure-activity relationship was studied. Analogs bearing methylsulfide and fluoride groups exhibited potency comparable to that of the parent compound HTI-286 and to paclitaxel in cytotoxicity assays against KB-3-1 cell lines. These analogs were more potent than paclitaxel against P-glycoprotein expressing KB-8-5 and KB-V1 cell lines. Several analogs showed strong inhibition of tubulin polymerization.
authors.affiliation: Chemical and Screening Sciences, Discovery Medicinal Chemistry, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. niuc@wyeth.com
authors.forename: Chuan
authors.initials: C
authors.lastname: Niu
authors.forename: Daniel
authors.initials: D
authors.lastname: Smith
authors.forename: Arie
authors.initials: A
authors.lastname: Zask
authors.forename: Frank
authors.initials: F
authors.lastname: Loganzo
authors.forename: Carolyn
authors.initials: C
authors.lastname: Discafani
authors.forename: Carl
authors.initials: C
authors.lastname: Beyer
authors.forename: Lee
authors.initials: L
authors.lastname: Greenberger
authors.forename: Semiramis
authors.initials: S
authors.lastname: Ayral-Kaloustian
mesh_terms: D002460:Cell Line; D006801:Humans; D008545:Melanoma / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D050257:Tubulin Modulators
chemical_list: C473896:HTI-286; D009842:Oligopeptides; D050257:Tubulin Modulators