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
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
Journal title :
Bioorganic & Medicinal Chemistry Letters
