Discovery and biological evaluation of novel alpha-glucosidase inhibitors with in vivo antidiabetic effect.
Discovery of alpha-glucosidase inhibitors has been actively pursued with the aim to develop therapeutics for the treatment of diabetes and the other carbohydrate-mediated diseases. We have identified four novel alpha-glucosidase inhibitors by means of a drug design protocol involving the structure-based virtual screening under consideration of the effects of ligand solvation in the scoring function and in vitro enzyme assay. Because the newly identified inhibitors reveal in vivo antidiabetic activity as well as a significant potency with more than 70% inhibition of the catalytic activity of alpha-glucosidase at 50 microM, all of them seem to deserve further development to discover new drugs for diabetes. Structural features relevant to the interactions of the newly identified inhibitors with the active site residues of alpha-glucosidase are discussed in detail.
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea. hspark@sejong.ac.kr
Hwangseo
H
Park
Kyo Yeol
KY
Hwang
Young Hoon
YH
Kim
Kyung Hwan
KH
Oh
Jae Yeon
JY
Lee
Keun
K
Kim
D020909:Acarbose / Q000737:chemistry; D000818:Animals; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003920:Diabetes Mellitus / Q000188:drug therapy*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley; D000520:alpha-Glucosidases / Q000737:chemistry
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D000520:alpha-Glucosidases; D020909:Acarbose