MOLECULAR DOCKING OF B-SITOSTEROL AND STIGMASTEROL ISOLATED FROM Morinda citrifolia WITH αAMYLASE, α-GLUCOSIDASE, DIPEPTIDYLPEPTIDASE-IV, AND PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-y
N. Lolok, D. S. F. Ramadhan, S. A. Sumiwi, I. Sahidin, J. Levita
Abstract
In Indonesia, Morinda citrifolia (Rubiaceae) fruit has been traditionally used to treat various diseases. A previous study confirmed the presence of flavonoids, terpenoids, alkaloids, and steroids in the ethanol and hexane extracts of M. citrifolia fruit. Our work studied the molecular interaction of -sitosterol and stigmasterol isolated from the fruit of this plant with α-amylase, α-glucosidase, PPAR-, and DPP-IV. The X-ray crystal structures of the proteins were downloaded from RCSB Protein Data Bank (https://www.rcsb.org/). The 3D structure of the ligands was obtained from the PubChem Compound databases (https://pubchem.ncbi.nlm.nih.gov/), subjected to energy minimization using the MMFF94 forcefield partial charges, and the torsions were set to default in the AutoDock tools program. The ligands were docked to the active binding site of the proteins. The results indicated that both stigmasterol and - sitosterol could occupy all binding sites of the proteins, but the best interaction (indicated by docking score) is with α-amylase (better than that of acarbose) and α-glucosidase (weaker to that of acarbose). In DPP-IV, -sitosterol occupies the S2 extensive subsite, similar to teneligliptin, a DPP-IV inhibitor. Stigmasterol builds one hydrogen bond with Val207 and occupies a similar location with -sitosterol. -sitosterol also interacts with Glu343 similarly as chiglitazar, a full agonist of PPAR-. Thus, -sitosterol might be able to be further developed as an anti-T2DM drug candidate by inhibiting α-amylase, α-glucosidase, DPP-IV, as well as activating PPAR-