Combinatorial Chemistry & High Throughput Screening

Author(s): Keith J. Stanger, Daniel Sliva, Jiahua Jiang and Viktor Krchnak

DOI: 10.2174/138620706778700161

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Synthesis and Screening of N-Alkyl Hydroxamates for Inhibition of Cancer Cell Proliferation

Page: [651 - 661] Pages: 11

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Abstract

A small library of N-alkylated amino acid-derived sulfonamide hydroxamates was synthesized on solid phase and tested for inhibition of proliferation of the highly invasive breast cancer cell line MDA-MB-231. The most active compound 4317 inhibited cell growth at IC50 30 μM. N-alkylation of N-H hydroxamate-based MMP inhibitors, a modification known to eliminate MMP activity, enhanced cell proliferation inhibition potency.

Keywords: MMP inhibitors, N-alkylation, Gly-derived hydroxamates, invasive breast cancer cells, pyridine derivative