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

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.