Title of article
Evaluation of new migrastatin and dorrigocin congeners unveils cell migration inhibitors with dramatically improved potency
Author/Authors
Jianhua Ju، نويسنده , , Scott R. Rajski، نويسنده , , Si-Kyu Lim، نويسنده , , Jeong-Woo Seo، نويسنده , , Noël R. Peters، نويسنده , , F. Michael Hoffmann، نويسنده , , Chia-Ben Shen، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
4
From page
5951
To page
5954
Abstract
Lactimidomycin (LTM, 1), iso-migrastatin (iso-MGS, 2) and migrastatin (MGS, 3) are macrolide antitumor antibiotics differing in macrolide ring size but all bearing a glutarimide side chain. To further develop these natural products and related analogs as drug candidates we have produced and evaluated the biological activities of a small library of iso-MGS and LTM-derived agents; congeners evaluated bear either the MGS scaffold or related acyclic (dorrigocin) scaffolds. Scratch wound-healing (SWH) assays with 4T1 mouse and MDA-MB-231 human mammary tumor cell lines, respectively, reveal structural elements crucial to inhibition of cell migration by these compounds. Moreover, two substances, 14 and 17, with activity far superior to that of MGS are unveiled by SWH assays.
Keywords
biosynthesis , Semi-synthesis , structure–activity relationship , drug discovery , macrolide , metastasis , cell migration , Scratch wound-healing (SWH) , Migrastatin , 14-Membered , Iso-migrastatin
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
800147
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