DPAGT1 Inhibitors of Capuramycin Analogues and Their Antimigratory Activities of Solid Tumors

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2020 Sep 4

PMID 32886511

Citations 4

Authors

Katsuhiko Mitachi

Rita G Kansal

Kirk E Hevener

Cody D Gillman

Syed M Hussain

Hyun Gi Yun

Gustavo A Miranda-Carboni

Evan S Glazer

William M Clemons Jr

Michio Kurosu

Affiliations

Soon will be listed here.

Abstract

Capuramycin displays a narrow spectrum of antibacterial activity by targeting bacterial translocase I (MraY). In our program of development of new -acetylglucosaminephosphotransferase1 (DPAGT1) inhibitors, we have identified that a capuramycin phenoxypiperidinylbenzylamide analogue (CPPB) inhibits DPAGT1 enzyme with an IC value of 200 nM. Despite a strong DPAGT1 inhibitory activity, CPPB does not show cytotoxicity against normal cells and a series of cancer cell lines. However, CPPB inhibits migrations of several solid cancers including pancreatic cancers that require high DPAGT1 expression in order for tumor progression. DPAGT1 inhibition by CPPB leads to a reduced expression level of Snail but does not reduce E-cadherin expression level at the IC (DPAGT1) concentration. CPPB displays a strong synergistic effect with paclitaxel against growth-inhibitory action of a patient-derived pancreatic adenocarcinoma, PD002: paclitaxel (IC: 1.25 μM) inhibits growth of PD002 at 0.0024-0.16 μM in combination with 0.10-2.0 μM CPPB (IC: 35 μM).

Citing Articles

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Antibacterial Activity of Pharmaceutical-Grade Rose Bengal: An Application of a Synthetic Dye in Antibacterial Therapies.

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