Synthesis of butyl-isobutyl-phthalate and its interaction with α-glucosidase in vitro.
Butyl-isobutyl-phthalate (BIP), isolated from the rhizoid of Laminaria japonica, is a potential α-glucosidase inhibitor for Type II diabetes treatment. In the present study, a synthetic route was established as a useful approach to obtain enough BIP. Fluorescence analysis, circular dichroism spectra and molecular docking methods were employed to elucidate the underlying molecular mechanisms of BIP inhibition on α-glucosidase. The results revealed that BIP could be synthesized in two steps and the synthesized BIP bound with α-glucosidase and induced conformational changes of the enzyme. The interaction between BIP and α-glucosidase was driven by both hydrophobic forces and hydrogen bond. The docking results indicated that the benzene ring and the isopropyl group of the BIP could fit into the hydrophobic pocket composed of Phe177, Phe157, Leu176, Leu218, Ala278 and the propyl group fitted into another nearby hydrophobic pocket formed by Trp154, Pro240, Leu174 and Ala162, respectively. This study provides useful information for the understanding of the BIP-α-glucosidase interaction and development of new α-glucosidase inhibitors.
Liu
Ming
M
Institute of Oceanology, Chinese Academy of Science, Qingdao 266071, China.
Zhang
Wei
W
Qiu
Lin
L
Lin
Xiukun
X
D065089:Glycoside Hydrolase Inhibitors; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010795:Phthalic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D000520:alpha-Glucosidases / Q000737:chemistry*
D065089:Glycoside Hydrolase Inhibitors; D010795:Phthalic Acids; C557975:butyl isobutyl phthalate; D000520:alpha-Glucosidases