Docking Study of Cardiovascular Diseases Treatment Drugs Salvianolic Acid A and C into the Activity Cavity of Intestinal UDP-Glucuronosyltransferase (UGT) 1A8

作者：Zhu, Ling-Min; Lin, Peng; Dai, Tao; Zhang, Chuan-Huan; Ma, Rui-Ping^*

来源：Latin American Journal of Pharmacy, 2017, 36(1): 179-183.

• cardiovascular diseases
• danshen
• salvianolic acid A/C
• in silico

Cardiovascular diseases remains to threaten the health of humans, and Danshen is a traditional Chinese herbal medicine widely used to treat cardiovascular diseases. Clinical herb-drug interaction during the therapy of cardiovascular diseases was evaluated in the present study. Two major ingredients salvianolic acid A and C from Danshen were docked into the activity cavity of UDP-glucuronosyltransferase (UGT) 1A8 which has been accepted to be an important UGT isoform, trying to indicate UGT1A8 inhibition-based herb-drug interaction. Homology modeling method was used to construct the crystal structure of UGT1A8, and Autodock Version 4.2 was used to dock the salvianolic acid A/C into the activity cavity of UGT1A8. The active pocket binding with salvianolic acid A/C consisted of the following amino acids residues: Gly35, Ser36, His37, Phe39, Leu83, Phe93, Asp95, Trp98, Leu105, Phe106, Ser107, Leu108, Phe109, Ser111, Ser112, Asp115, Phe116, Arg170, Ser303, Ser306, Met307, Arg333, Gln354, Phe366, His369, Ala370, Gly371, Ser372, His373, Gly374, Phe391, Asp393, and Gln394. The hydrogen bonds were formed between salvianolic acid A/C and some amino acids residues located in the activity cavity of UGT1A8. Salvianolic acid A formed five hydrogen bonds with four amino acids residues in the binding pocket of UGT1A8, including N atom of Ser36, NH1 atom of Arg170, OD1 and 002 atoms of Asp393, and ND1 atom of His373. Salvianolic acid C formed seven hydrogen bonds to five residues, including 001 atom of Asp95, OG atom of Ser112, OG atom of Ser306, NH1 atom of Arg333, and OE1 atom of Gln354. Besides the hydrogen bonds, Salvianolic acid A and C also formed hydrophobic interactions with the activity cavity of UGT1A8. Salvianolic acid A formed hydrophobic contacts with non-charged polar residues Ser36, Ser112, Ser306, Gly371, charged residues His37, His169, His373, Asp393, and non-polar residues Trp98, Leu105, Phe109, Phe116, Met307, Phe391. Salvianolic acid C formed hydrophobic contacts to non-charged polar residues Ser112, Gly115, Ser306, Gln354, Gly371, charged residues His369, His373, non-polarresidues Phe39, Leu83, Trp98, Leu105, Phe116, Met307, Phe391. In conclusion, the present study demonstrated the inhibition of salvianolic acid A/C on the activity of UGT1A8 using in silkco docking method.

• 出版日期2017-1
• 单位烟台毓璜顶医院; 青岛大学; 山东省千佛山医院