Design and Synthesis of α-Glucosidase Inhibitor Having DNA Cleaving Activity

Abstract

Apoptosis, or programmed cell death, is a mechanism by which cells undergo death to control cell proliferation or in response to DNA damage. The present study was designed to explore small molecule apoptosis inducers for antitumor agents. The synthesis of 4-sulfonylphenyl α-D-glucopyranoside derivatives 1-6 and 4-(sulfonylamino)phenyl α-D-glucopyranoside derivatives 7-12, endoplasmic reticulum (ER)-targeted small molecules that were designed to induce apoptosis from ER stress by ER glucosidase inhibition and DNA damage is described. Compounds 6 and 12, with a terminal 2-naphthyl group, indicated inhibitions of α-glucosidases from S. cerevisiae (IC₅₀=51.7 μM and IC₅₀=74.1 μM) and B. stearothermophilus (IC₅₀=60.1 μM and IC₅₀=89.1 μM). Moreover, compound 12 strongly induced the DNA strand breakage condition. When compounds 1-12 were assayed for their ability to inhibit processing by glucosidases at the cellular level, no effects on glycoprotein processing were observed.