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 IC(50) 30 microM. N-alkylation of N-H hydroxamate-based MMP inhibitors, a modification known to eliminate MMP activity, enhanced cell proliferation inhibition potency.
Stanger
Keith J
KJ
Department of Chemistry and Biochemistry, 251 Nieuwland Science Center, University of Notre Dame, Notre Dame, IN 46556, USA.
Sliva
Daniel
D
Jiang
Jiahua
J
Krchnák
Viktor
V
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002853:Chromatography, Liquid; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids