Ligand compatibility of salacinol-type α-glucosidase inhibitors toward the GH31 family

Fumihiro Ishikawa; Aiko Hirano; Yuuto Yoshimori; Kana Nishida; Shinya Nakamura; Katsuki Takashima; Shinsuke Marumoto; Kiyofumi Ninomiya; Isao Nakanishi; Weijia Xie; Toshio Morikawa; Osamu Muraoka; Genzoh Tanabe

doi:10.1039/d0ra10038b

Ligand compatibility of salacinol-type α-glucosidase inhibitors toward the GH31 family

RSC Adv. 2021 Jan 15;11(6):3221-3225. doi: 10.1039/d0ra10038b. eCollection 2021 Jan 14.

Authors

Affiliations

¹ Pharmaceutical Organic Chemistry Lab, Faculty of Pharmacy, Kindai University 3-4-1 Kowakae Higashi-Osaka Osaka 577-8502 Japan.
² Computational Drug Design and Discovery Lab, Faculty of Pharmacy, Kindai University 3-4-1 Kowakae Higashi-Osaka Osaka 577-8502 Japan.
³ Joint Research Center, Kindai University 3-4-1 Kowakae Higashi-Osaka Osaka 577-8502 Japan.
⁴ Pharmaceutical Research and Technology Institute, Kindai University 3-4-1 Kowakae Higashi-Osaka Osaka 577-8502 Japan.
⁵ State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, China Pharmaceutical University Nanjing 2100009 P. R. China g-tanabe@phar.kindai.ac.jp.

Abstract

We show that salacinol-type α-glucosidase inhibitors are ligand-compatible with the GH 31 family. Salacinol and its 3'-O-benzylated analogs inhibit human lysosomal α-glucosidase at submicromolar levels. Simple structure-activity relationship studies reveal that the salacinol side-chain stereochemistry significantly influences binding to GH31 α-glucosidases.