2. Academic Validation
  3. Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents

Tubulin inhibitors. Synthesis and biological activity of HTI-286 analogs with B-segment heterosubstituents

  • Bioorg Med Chem Lett. 2004 Aug 16;14(16):4329-32. doi: 10.1016/j.bmcl.2004.05.077.
Chuan Niu 1,  Daniel Smith,  Arie Zask,  Frank Loganzo,  Carolyn Discafani,  Carl Beyer,  Lee Greenberger,  Semiramis Ayral-Kaloustian
Affiliations

Affiliation

  • 1 Chemical and Screening Sciences, Discovery Medicinal Chemistry, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. [email protected]
PMID: 15261296 DOI: 10.1016/j.bmcl.2004.05.077
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.

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