Design and synthesis of alpha-glucosidase inhibitor having DNA cleaving activity
2006
Hakamata, W.(National Inst. of Health Science, Tokyo (Japan)) | Yamamoto, E. | Muroi, M. | Mochizuki, M. | Kurihara, M. | Okuda, H. | Fukuhara, K.
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-sulfionylphenyl alpha-D-glucopyranoside derivatives 1-6 and 4-(sulfonylamino)phenyl alpha-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 aglucosidases from S. cerevisiae (ICsub(50)=51.7 microM and ICsub(50)=74.1 microM) and B. stearothermophilus (ICsub(50)=60.1 microM and ICsub(50)=89.1 microM). 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.
Показать больше [+] Меньше [-]