SCREENING NATURAL PRODUCT COMPOUNDS FROM CLEISTOCALYX OPERCULATUS FOR PROTEIN TYROSINE PHOSPHATASE 1B INHIBITORY ACTIVITY BY USING MOLECULAR DOCKING METHOD

Abstract

Background: Diabetes mellitus is a complex chronic disease. It is characterized by high level of glucose in the blood, caused by deficiency in insulin secretion from the β pancreatic’s cells or the operability of insulin. The protein tyrosine phosphatase 1B (PTP1B) catalyzes in order to remove of the phosphate group from the insulin receptor's phosphotyrosine, so it reduces the effects of insulin on target tissues. Therefore, inhibiting this enzyme is an effective method to treat diabetes mellitus. Cleistocalyx operculatus has been shown to be effective with the treatment of diabetes mellitus. Objectives: In this study, we evaluated the inhibitory effects of PTP1B enzyme of Cleistocalyx operculatus’s compounds by using molecular docking method. Materials and Methods: The protein tyrosin protease 1B structure was obtained from Protein Data Bank. Compounds were collected from the publication of Cleistocalyx operculatus and these structures were obtained from the PubChem database. Molecular docking was done by Autodock vina software. Lipinski Rule of Five is used to compare compounds with drug-like and non-drug-like properties. Pharmacokinetic parameters of potential compounds were evaluated using the pkCSM tool. Results: Based on previous publication of Cleistocalyx operculatus, we have collected 62 compounds. The results showed that there are 4 compounds have PTP1B inhibitory effect stronger than the positive control including abieta-7,13-diene, kaempferol, quercetin, luteolin. Analysising Lipinski rule of five showed that all 4 compounds have drug-likeness propieties. Moreover, predict ADMET showed that these compounds have good intestinal absorption and low toxicity. Conclusion: Therefore, kaempferol, quercetin, luteolin and abieta-7,13-diene may be potential natural product compound for diatetes treatment.