02214nas a2200229 4500008004100000245009500041210006900136260001600205300001400221490000700235520155200242653001101794653001201805653002201817653001401839653000901853653002201862100002301884700002501907700001701932856003501949 2018 eng d00aVirtual Screening of Indonesian Herbal Database as Murine Double Minute-2 (MDM2) Inhibitor0 aVirtual Screening of Indonesian Herbal Database as Murine Double cAugust 2018 a1184-11890 v103 a

Background: Murine Double Minute-2 (MDM2) overexpression causes the p53 deficiency, so the role p53 as a cell regulator does not work in the case of cancer. Methods: In this study, virtual screening of Indonesian herbal database to discover MDM2 inhibitors was carried out. Autodock and Autodock Vina validated with Directory of Useful Decoy-Enhanced (DUD-E). Validation parameters were performed with Enrichment Factor, Receiver Operating Characteristics, and Area Under Curve. Results: The validation with the grid box 70x70x70 on Autodock resulting AUC value 0.72, while in Autodock Vina 0.43. Autodock Vina did not fulfilll the standard value but still used for comparison. Based on the virtual screening result, top ten compounds from Autodock are Nimolicinol, Jacoumaric acid, Isoarborinol, Lantic acid, Diosgenin, Theasaponin E1, Taraxasterol, Leucadenone C, Simiarenol, and Alpha-Amyrin were found to have strong interaction with MDM2, with binding energy (ΔG) ranging from -8.83 to -9.65 kcal/mol. The Autodock Vina screening resulted in the identification of Yuehchukene, Morusin, Cyanidin, Leucadenone C, Roxburghine-B, Ocidentoside, Beta-sitosterol, Curine, Withangulatin, and Jacoumaric acid as potential inhibitors with binding energy (ΔG) ranging from -8.7 to -9.4 kcal/mol. Conclusion: Jacoumaric acid and Leucadenone C were shown to interact with the active site in MDM2 at residues Leu54, Ile61, Met62, and Ile99.

10aCancer10aDocking10aIndonesian Herbal10aInhibitor10aMDM210aVirtual Screening1 aVictory, Alexander1 aSyahdi, Rezi, Riadhi1 aYanuar, Arry uhttps://phcogj.com/article/738